메뉴 건너뛰기




Volumn 37, Issue 9, 2016, Pages 1403-1435

Current pharmacotherapy and putative disease-modifying therapy for Alzheimer’s disease

Author keywords

Alzheimer s; Amyloid plaques; Cognition; Disease modifying; Hallmarks; Pharmacotherapy

Indexed keywords

ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; APIGENIN; AVAGACESTAT; BAPINEUZUMAB; BETA SECRETASE INHIBITOR; CHOLINE ACETYLTRANSFERASE; DONEPEZIL; EPIGALLOCATECHIN GALLATE; FLAVONOID; FLURBIPROFEN; FUROCOUMARIN; GALANTAMINE; HARMINE; HOMOTAURINE; HYMENIALDISINE; KAEMPFEROL; LITHIUM; MEMANTINE; METHYLENE BLUE; MORIN; MYRICETIN; PENTOSALEN; QUERCETIN; RIVASTIGMINE; SEMAGACESTAT; STATINE DERIVATIVE; TACRINE; TARENFLURBIL; ACETYLCHOLINESTERASE; AMYLOID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUROLEPTIC AGENT;

EID: 84973130761     PISSN: 15901874     EISSN: 15903478     Source Type: Journal    
DOI: 10.1007/s10072-016-2625-7     Document Type: Review
Times cited : (69)

References (206)
  • 1
    • 84983532223 scopus 로고    scopus 로고
    • National Institute of Health. Accessed 10 Nov 2015
    • National Institute of Health. MedlinePlus: Alzheimer’s disease. http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html. Accessed 10 Nov 2015
    • (2015) MedlinePlus: Alzheimer’s disease
  • 2
    • 84990836205 scopus 로고    scopus 로고
    • National Institute on Aging. Alzheimer’s Disease Fact Sheet. Accessed 10 Nov
    • National Institute on Aging. Alzheimer’s Disease Education and Referral Center. Alzheimer’s Disease Fact Sheet. http://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet. Accessed 10 Nov 2015
    • (2015) Alzheimer’s Disease Education and Referral Center
  • 3
    • 84943277916 scopus 로고    scopus 로고
    • Alzheimer’s Disease Education and Referral Center. Accessed 10 Nov
    • Alzheimer’s Disease Education and Referral Center. About Alzheimer’s disease: Alzheimer’s basics. https://www.nia.nih.gov/alzheimers/topics/alzheimers-basics. Accessed 10 Nov 2015
    • (2015) About Alzheimer’s disease: Alzheimer’s basics
  • 4
    • 84949805790 scopus 로고    scopus 로고
    • NIH Senior Health. Accessed 14 Nov
    • NIH Senior Health. Alzheimer’s disease. http://nihseniorhealth.gov/alzheimersdisease/whatisalzheimersdisease/01.html. Accessed 14 Nov 2015
    • (2015) Alzheimer’s disease
  • 6
    • 0032894121 scopus 로고    scopus 로고
    • The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease
    • COI: 1:CAS:528:DyaK1MXivVyqt7g%3D, PID: 10214737
    • Delacourte A, David JP, Sergeant N, Buee L, Wattez A, Vermersch P et al (1999) The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease. Neurology 52:1158–1165
    • (1999) Neurology , vol.52 , pp. 1158-1165
    • Delacourte, A.1    David, J.P.2    Sergeant, N.3    Buee, L.4    Wattez, A.5    Vermersch, P.6
  • 8
    • 80053971718 scopus 로고    scopus 로고
    • Current and emerging drug treatment options for Alzheimer’s disease: a systematic review
    • COI: 1:CAS:528:DC%2BC3MXhs1SlsbbI, PID: 21985169
    • Herrmann N, Chau SA, Kircanski I, Lanctot KL (2011) Current and emerging drug treatment options for Alzheimer’s disease: a systematic review. Drugs 71:2031–2065
    • (2011) Drugs , vol.71 , pp. 2031-2065
    • Herrmann, N.1    Chau, S.A.2    Kircanski, I.3    Lanctot, K.L.4
  • 9
    • 3242737470 scopus 로고    scopus 로고
    • Challenging the amyloid cascade hypothesis: senile plaques and amyloid-beta as protective adaptations to Alzheimer disease
    • Lee HG, Casadesus G, Zhu X, Takeda A, Perry G, Smith MA (2014) Challenging the amyloid cascade hypothesis: senile plaques and amyloid-beta as protective adaptations to Alzheimer disease. Ann N Y Acad Sci 1019:1–4
    • (2014) Ann N Y Acad Sci , vol.1019 , pp. 1-4
    • Lee, H.G.1    Casadesus, G.2    Zhu, X.3    Takeda, A.4    Perry, G.5    Smith, M.A.6
  • 10
    • 84886631402 scopus 로고
    • Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue
    • COI: 1:CAS:528:DyaE1cXkvVKmug%3D%3D, PID: 144789
    • Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE (1977) Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J Neurol Sci 34:247–265
    • (1977) J Neurol Sci , vol.34 , pp. 247-265
    • Perry, E.K.1    Gibson, P.H.2    Blessed, G.3    Perry, R.H.4    Tomlinson, B.E.5
  • 11
    • 0017652462 scopus 로고
    • Memory and cognitive function in man: does the cholinergic system have a specific role?
    • COI: 1:STN:280:DyaE2s3jtlSisw%3D%3D, PID: 560649
    • Drachman D (1977) Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 27:783–790
    • (1977) Neurology , vol.27 , pp. 783-790
    • Drachman, D.1
  • 12
    • 0015965912 scopus 로고
    • Human memory and the cholinergic system. A relationship to aging?
    • COI: 1:CAS:528:DyaE2cXhsVWhs7o%3D, PID: 4359364
    • Drachman D, Leavitt J (1974) Human memory and the cholinergic system. A relationship to aging? Arch Neurol 30:113–121
    • (1974) Arch Neurol , vol.30 , pp. 113-121
    • Drachman, D.1    Leavitt, J.2
  • 13
    • 0020072221 scopus 로고
    • Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain
    • COI: 1:STN:280:DyaL387ivFWntQ%3D%3D, PID: 7058341
    • Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239
    • (1982) Science , vol.215 , pp. 1237-1239
    • Whitehouse, P.J.1    Price, D.L.2    Struble, R.G.3    Clark, A.W.4    Coyle, J.T.5    Delon, M.R.6
  • 15
    • 0026756286 scopus 로고
    • A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease
    • COI: 1:STN:280:DyaK3s%2FisVOgtg%3D%3D, PID: 1406817
    • Davis KL, Thal LJ, Gamzu ER, Davis CS, Woolson RF, Gracon SI et al (1992) A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease. N Engl J Med 327:1253–1259
    • (1992) N Engl J Med , vol.327 , pp. 1253-1259
    • Davis, K.L.1    Thal, L.J.2    Gamzu, E.R.3    Davis, C.S.4    Woolson, R.F.5    Gracon, S.I.6
  • 16
    • 0032910197 scopus 로고    scopus 로고
    • The cholinergic hypothesis of Alzheimer’s disease: a review of progress
    • COI: 1:STN:280:DyaK1M7mvVKnuw%3D%3D, PID: 10071091
    • Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66:137–147
    • (1999) J Neurol Neurosurg Psychiatry , vol.66 , pp. 137-147
    • Francis, P.T.1    Palmer, A.M.2    Snape, M.3    Wilcock, G.K.4
  • 17
    • 0033591017 scopus 로고    scopus 로고
    • Cholinergic markers in elderly patients with early signs of Alzheimer disease
    • COI: 1:STN:280:DyaK1M3jtFCjug%3D%3D, PID: 10217056
    • Davis KL, Mohs RC, Marin D (1999) Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 281:1401–1406
    • (1999) JAMA , vol.281 , pp. 1401-1406
    • Davis, K.L.1    Mohs, R.C.2    Marin, D.3
  • 18
    • 0033590969 scopus 로고    scopus 로고
    • Challenging the cholinergic hypothesis in Alzheimer disease
    • COI: 1:STN:280:DyaK1M3jtFCisQ%3D%3D, PID: 10217061
    • Davies P (1999) Challenging the cholinergic hypothesis in Alzheimer disease. JAMA 281:1433–1434
    • (1999) JAMA , vol.281 , pp. 1433-1434
    • Davies, P.1
  • 19
    • 0033922730 scopus 로고    scopus 로고
    • Evolution of Alzheimer’s disease-related cytoskeletal changes in the basal nucleus of meynert
    • COI: 1:STN:280:DC%2BD3M%2FntVyisA%3D%3D, PID: 10965795
    • Sassin I, Schultz C, Thal DR, Rub U, Arai K, Braak E et al (2000) Evolution of Alzheimer’s disease-related cytoskeletal changes in the basal nucleus of meynert. Acta Neuropathol 100:259–269
    • (2000) Acta Neuropathol , vol.100 , pp. 259-269
    • Sassin, I.1    Schultz, C.2    Thal, D.R.3    Rub, U.4    Arai, K.5    Braak, E.6
  • 20
    • 34548672350 scopus 로고    scopus 로고
    • Cholinotrophicmolecular substrates of mild cognitive impairment in the elderly
    • COI: 1:CAS:528:DC%2BD2sXhtlSitL7O, PID: 17908035
    • Mufson EJ, Counts SE, Fahnestock M, Ginsberg SD (2007) Cholinotrophicmolecular substrates of mild cognitive impairment in the elderly. Curr Alzheimer Res 4:340–350
    • (2007) Curr Alzheimer Res , vol.4 , pp. 340-350
    • Mufson, E.J.1    Counts, S.E.2    Fahnestock, M.3    Ginsberg, S.D.4
  • 21
    • 0026562382 scopus 로고
    • Convergent cholinergic activities in aging and Alzheimer’s disease
    • COI: 1:STN:280:DyaK38zis12ntQ%3D%3D, PID: 1625768
    • Perry EK, Johnson M, Kerwin JM, Piggott MA, Court JA, Shaw PJ et al (1992) Convergent cholinergic activities in aging and Alzheimer’s disease. Neurobiol Aging 13:393–400
    • (1992) Neurobiol Aging , vol.13 , pp. 393-400
    • Perry, E.K.1    Johnson, M.2    Kerwin, J.M.3    Piggott, M.A.4    Court, J.A.5    Shaw, P.J.6
  • 22
    • 79955738773 scopus 로고    scopus 로고
    • The history of the cholinergic hypothesis
    • COI: 1:CAS:528:DC%2BC3MXmtFClur4%3D, PID: 20060018
    • Contestabile A (2011) The history of the cholinergic hypothesis. Behav Brain Res 221:334–340
    • (2011) Behav Brain Res , vol.221 , pp. 334-340
    • Contestabile, A.1
  • 23
    • 0020634081 scopus 로고
    • Loss of neurons in the nucleus basalis of meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s disease
    • COI: 1:STN:280:DyaL2c%2FkvVaksg%3D%3D, PID: 6637393
    • Arendt T, Bigl V, Arendt A, Tennstedt A (1983) Loss of neurons in the nucleus basalis of meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s disease. Acta Neuropathol 61:101–108
    • (1983) Acta Neuropathol , vol.61 , pp. 101-108
    • Arendt, T.1    Bigl, V.2    Arendt, A.3    Tennstedt, A.4
  • 24
    • 0028947094 scopus 로고
    • Ageing: the cholinergic hypothesis of cognitive decline
    • COI: 1:CAS:528:DyaK2MXlsVGit7o%3D, PID: 7620303
    • Gallagher M, Colombo PJ (1995) Ageing: the cholinergic hypothesis of cognitive decline. Curr Opin Neurobiol 5:161–168
    • (1995) Curr Opin Neurobiol , vol.5 , pp. 161-168
    • Gallagher, M.1    Colombo, P.J.2
  • 25
    • 0033600274 scopus 로고    scopus 로고
    • Translating cell biology into therapeutic advances in Alzheimer’s disease
    • COI: 1:CAS:528:DyaK1MXktlejsLg%3D, PID: 10392577
    • Selkoe DJ (1999) Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature 399:A23–A31
    • (1999) Nature , vol.399 , pp. A23-A31
    • Selkoe, D.J.1
  • 26
    • 0026423215 scopus 로고
    • Alzheimer’s disease in the beginning
    • COI: 1:STN:280:DyaK38%2Fos1Sguw%3D%3D, PID: 1684220
    • Selkoe DJ (1991) Alzheimer’s disease in the beginning. Nature 354:432–433
    • (1991) Nature , vol.354 , pp. 432-433
    • Selkoe, D.J.1
  • 27
    • 0023105114 scopus 로고
    • The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor
    • COI: 1:CAS:528:DyaL2sXktVWkt7s%3D, PID: 2881207
    • Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH et al (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–736
    • (1987) Nature , vol.325 , pp. 733-736
    • Kang, J.1    Lemaire, H.G.2    Unterbeck, A.3    Salbaum, J.M.4    Masters, C.L.5    Grzeschik, K.H.6
  • 28
    • 0028170818 scopus 로고
    • Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer’s disease
    • COI: 1:CAS:528:DyaK2MXitlSnsb4%3D, PID: 7888181
    • Selkoe DJ (1994) Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer’s disease. Annu Rev Cell Biol 10:373–403
    • (1994) Annu Rev Cell Biol , vol.10 , pp. 373-403
    • Selkoe, D.J.1
  • 29
    • 0038117796 scopus 로고    scopus 로고
    • Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline
    • COI: 1:CAS:528:DC%2BD3cXisVeiu7c%3D, PID: 10735393
    • Naslund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P et al (2000) Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA 283:1571–1577
    • (2000) JAMA , vol.283 , pp. 1571-1577
    • Naslund, J.1    Haroutunian, V.2    Mohs, R.3    Davis, K.L.4    Davies, P.5    Greengard, P.6
  • 30
    • 33947247360 scopus 로고    scopus 로고
    • BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice
    • COI: 1:CAS:528:DC%2BD2sXjsVGhsrg%3D, PID: 17258906
    • Ohno M, Cole SL, Yasvoina M, Zhao J, Citron M, Berry R et al (2007) BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Neurobiol Dis 26:134–145
    • (2007) Neurobiol Dis , vol.26 , pp. 134-145
    • Ohno, M.1    Cole, S.L.2    Yasvoina, M.3    Zhao, J.4    Citron, M.5    Berry, R.6
  • 31
    • 0035066332 scopus 로고    scopus 로고
    • Alzheimer’s disease: genes, proteins and therapy
    • COI: 1:CAS:528:DC%2BD3MXislCrsLc%3D, PID: 11274343
    • Selkoe DJ (2001) Alzheimer’s disease: genes, proteins and therapy. Physiol Rev 81:741–766
    • (2001) Physiol Rev , vol.81 , pp. 741-766
    • Selkoe, D.J.1
  • 32
    • 0033613129 scopus 로고    scopus 로고
    • Cellular mechanisms of beta-amyloid production and secretion
    • COI: 1:CAS:528:DyaK1MXmvVCntLc%3D, PID: 10500121
    • Sinha S, Lieberburg I (1999) Cellular mechanisms of beta-amyloid production and secretion. Proc Natl Acad Sci USA 96:11049–11053
    • (1999) Proc Natl Acad Sci USA , vol.96 , pp. 11049-11053
    • Sinha, S.1    Lieberburg, I.2
  • 33
    • 0027459686 scopus 로고
    • Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide
    • COI: 1:CAS:528:DyaK3sXitFSltr0%3D, PID: 7678698
    • Seubert P, Oltersdorf T, Lee MG, Barbour R, Blomquist C, Davis DL (1993) Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide. Nature 361:260–263
    • (1993) Nature , vol.361 , pp. 260-263
    • Seubert, P.1    Oltersdorf, T.2    Lee, M.G.3    Barbour, R.4    Blomquist, C.5    Davis, D.L.6
  • 34
    • 0001181116 scopus 로고    scopus 로고
    • Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics
    • COI: 1:CAS:528:DC%2BD3sXitFWqt74%3D
    • Selkoe DJ, Schenk D (2003) Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics. Ann Rev Pharmacol Toxicol 43:545–584
    • (2003) Ann Rev Pharmacol Toxicol , vol.43 , pp. 545-584
    • Selkoe, D.J.1    Schenk, D.2
  • 35
    • 0026907151 scopus 로고
    • A pathogenic mutation for probable Alzheimer’s disease in the APP Gene at the N-terminus of beta-amyloid
    • COI: 1:CAS:528:DyaK38XlsVyms7o%3D, PID: 1302033
    • Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B et al (1992) A pathogenic mutation for probable Alzheimer’s disease in the APP Gene at the N-terminus of beta-amyloid. Nat Genet 1:345–347
    • (1992) Nat Genet , vol.1 , pp. 345-347
    • Mullan, M.1    Crawford, F.2    Axelman, K.3    Houlden, H.4    Lilius, L.5    Winblad, B.6
  • 36
    • 0028099612 scopus 로고
    • Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the swedish familial Alzheimer disease mutation
    • COI: 1:CAS:528:DyaK2MXisFyqtLc%3D, PID: 7991571
    • Citron M, Vigo-Pelfrey C, Teplow DB, Miller C, Schenk D, Johnston J et al (1994) Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the swedish familial Alzheimer disease mutation. Proc Natl Acad Sci USA 91:11993–11997
    • (1994) Proc Natl Acad Sci USA , vol.91 , pp. 11993-11997
    • Citron, M.1    Vigo-Pelfrey, C.2    Teplow, D.B.3    Miller, C.4    Schenk, D.5    Johnston, J.6
  • 37
    • 0030007964 scopus 로고    scopus 로고
    • Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation
    • COI: 1:CAS:528:DyaK28Xis1Kqt7k%3D, PID: 9173910
    • Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ (1996) Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis 3:16–32
    • (1996) Neurobiol Dis , vol.3 , pp. 16-32
    • Lemere, C.A.1    Blusztajn, J.K.2    Yamaguchi, H.3    Wisniewski, T.4    Saido, T.C.5    Selkoe, D.J.6
  • 38
  • 39
    • 0021207461 scopus 로고
    • Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein
    • COI: 1:CAS:528:DyaL2cXlt1ygtL4%3D, PID: 6236805
    • Glenner GG, Wong CW (1984) Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135
    • (1984) Biochem Biophys Res Commun , vol.122 , pp. 1131-1135
    • Glenner, G.G.1    Wong, C.W.2
  • 41
    • 0037174618 scopus 로고    scopus 로고
    • Alzheimer’s disease is a synaptic failure
    • COI: 1:CAS:528:DC%2BD38XotFSnur0%3D, PID: 12399581
    • Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298:789–791
    • (2002) Science , vol.298 , pp. 789-791
    • Selkoe, D.J.1
  • 42
    • 30344485665 scopus 로고    scopus 로고
    • Targeting acetylcholinesterase and butyrylcholinesterase in dementia
    • COI: 1:CAS:528:DC%2BD28Xht1ehtw%3D%3D, PID: 16083515
    • Lane RM, Potkin SG, Enz A (2006) Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol 9:101–124
    • (2006) Int J Neuropsychopharmacol , vol.9 , pp. 101-124
    • Lane, R.M.1    Potkin, S.G.2    Enz, A.3
  • 43
    • 0029863697 scopus 로고    scopus 로고
    • Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme
    • COI: 1:CAS:528:DyaK28XislCmsLk%3D, PID: 8608006
    • Inestrosa NC, Alvarez A, Pérez CA, Moreno RD, Vicente M, Linker C et al (1996) Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme. Neuron 16:881–891
    • (1996) Neuron , vol.16 , pp. 881-891
    • Inestrosa, N.C.1    Alvarez, A.2    Pérez, C.A.3    Moreno, R.D.4    Vicente, M.5    Linker, C.6
  • 44
    • 0033524414 scopus 로고    scopus 로고
    • Substrate binding to the peripheral site of acetylcholinesterase initiates enzymatic catalysis. Substrate inhibition arises as a secondary effect
    • COI: 1:CAS:528:DyaK1cXnvVKlsL8%3D, PID: 9890890
    • Szegletes T, Mallender WD, Thomas PJ, Rosenberry TL (1999) Substrate binding to the peripheral site of acetylcholinesterase initiates enzymatic catalysis. Substrate inhibition arises as a secondary effect. Biochemistry 38:122–133
    • (1999) Biochemistry , vol.38 , pp. 122-133
    • Szegletes, T.1    Mallender, W.D.2    Thomas, P.J.3    Rosenberry, T.L.4
  • 45
    • 0028270692 scopus 로고
    • Acetylcholinesterase peripheral anionic site degeneracy conferred by amino acid arrays sharing a common core
    • COI: 1:CAS:528:DyaK2cXitl2isrw%3D, PID: 8119978
    • Barak D, Kronman C, Ordentlich A, Ariel N, Bromberg A, Marcus D et al (1994) Acetylcholinesterase peripheral anionic site degeneracy conferred by amino acid arrays sharing a common core. J Biol Chem 269:6296–6305
    • (1994) J Biol Chem , vol.269 , pp. 6296-6305
    • Barak, D.1    Kronman, C.2    Ordentlich, A.3    Ariel, N.4    Bromberg, A.5    Marcus, D.6
  • 46
    • 34547795897 scopus 로고    scopus 로고
    • Acetylcholinesterases-the structural similarities and differences
    • COI: 1:CAS:528:DC%2BD2sXosVSht78%3D, PID: 17847707
    • Wiesner J, Kriz Z, Kuca K, Jun D, Koca J (2007) Acetylcholinesterases-the structural similarities and differences. J Enzyme Inhib Med Chem 22:417–424
    • (2007) J Enzyme Inhib Med Chem , vol.22 , pp. 417-424
    • Wiesner, J.1    Kriz, Z.2    Kuca, K.3    Jun, D.4    Koca, J.5
  • 48
    • 0029983531 scopus 로고    scopus 로고
    • The effect of cholinesterase inhibitors on the secretion of apps from rat brain cortex
    • COI: 1:CAS:528:DyaK28XjtVCksrw%3D, PID: 8624119
    • Giacobini E, Mori F, Lai CC (1996) The effect of cholinesterase inhibitors on the secretion of apps from rat brain cortex. Ann N Y Acad Sci 777:393–398
    • (1996) Ann N Y Acad Sci , vol.777 , pp. 393-398
    • Giacobini, E.1    Mori, F.2    Lai, C.C.3
  • 49
    • 84983532251 scopus 로고    scopus 로고
    • Alzheimer’s Association. Accessed 15 Dec
    • Alzheimer’s Association. FDA approved treatments for Alzheimer’s disease. http://www.alz.org/dementia/downloads/topicsheet_treatments.pdf. Accessed 15 Dec 2015
    • (2015) FDA approved treatments for Alzheimer’s disease
  • 50
    • 0028270519 scopus 로고
    • A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The tacrine study group
    • COI: 1:STN:280:DyaK2c7oslWmsQ%3D%3D, PID: 8139083
    • Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI (1994) A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The tacrine study group. JAMA 271:985–991
    • (1994) JAMA , vol.271 , pp. 985-991
    • Knapp, M.J.1    Knopman, D.S.2    Solomon, P.R.3    Pendlebury, W.W.4    Davis, C.S.5    Gracon, S.I.6
  • 51
    • 47849119964 scopus 로고    scopus 로고
    • Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis
    • COI: 1:CAS:528:DC%2BD1cXpt1WqtLw%3D, PID: 18686744
    • Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE (2008) Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 3:211–225
    • (2008) Clin Interv Aging , vol.3 , pp. 211-225
    • Hansen, R.A.1    Gartlehner, G.2    Webb, A.P.3    Morgan, L.C.4    Moore, C.G.5    Jonas, D.E.6
  • 52
    • 84885816253 scopus 로고    scopus 로고
    • Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection
    • COI: 1:CAS:528:DC%2BC3sXhvFOqtbfP, PID: 24148993
    • Singh M, Kaur M, Kukreja H, Chugh R, Silakari O, Singh D (2013) Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection. Eur J Med Chem 70:165–188
    • (2013) Eur J Med Chem , vol.70 , pp. 165-188
    • Singh, M.1    Kaur, M.2    Kukreja, H.3    Chugh, R.4    Silakari, O.5    Singh, D.6
  • 53
    • 33947206537 scopus 로고    scopus 로고
    • Acetylcholinesterase inhibitors from plants
    • COI: 1:CAS:528:DC%2BD2sXmtFKmsbk%3D, PID: 17346955
    • Mukherjee PK, Kumar V, Mal M, Houghton PJ (2007) Acetylcholinesterase inhibitors from plants. Phytomedicine 14:289–300
    • (2007) Phytomedicine , vol.14 , pp. 289-300
    • Mukherjee, P.K.1    Kumar, V.2    Mal, M.3    Houghton, P.J.4
  • 54
    • 0030052030 scopus 로고    scopus 로고
    • Learning deficits induced by chronic intraventricular infusion of quinolinic acid-protection by MK-801 and memantine
    • COI: 1:CAS:528:DyaK28XkslKqtw%3D%3D, PID: 8720470
    • Misztal M, Frankiewicz T, Parsons CG, Danysz W (1996) Learning deficits induced by chronic intraventricular infusion of quinolinic acid-protection by MK-801 and memantine. Eur J Pharmacol 296:1–8
    • (1996) Eur J Pharmacol , vol.296 , pp. 1-8
    • Misztal, M.1    Frankiewicz, T.2    Parsons, C.G.3    Danysz, W.4
  • 55
    • 15044338779 scopus 로고    scopus 로고
    • Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults
    • PID: 15717010
    • Lipton SA (2004) Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx 1:101–110
    • (2004) NeuroRx , vol.1 , pp. 101-110
    • Lipton, S.A.1
  • 57
    • 0030029425 scopus 로고    scopus 로고
    • Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices
    • COI: 1:CAS:528:DyaK28XhsVersL8%3D, PID: 8646415
    • Frankiewicz T, Potier B, Bashir ZI, Collingridge GL, Parsons CG (1996) Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices. Br J Pharmacol 117:689–697
    • (1996) Br J Pharmacol , vol.117 , pp. 689-697
    • Frankiewicz, T.1    Potier, B.2    Bashir, Z.I.3    Collingridge, G.L.4    Parsons, C.G.5
  • 58
    • 55949126654 scopus 로고    scopus 로고
    • Memantine protects rat cortical cultured neurons against β-amyloid-induced toxicity by attenuating tau phosphorylation
    • COI: 1:STN:280:DC%2BD1cjnvVOhsQ%3D%3D, PID: 19046381
    • Song MS, Rauw G, Baker GB, Kar S (2008) Memantine protects rat cortical cultured neurons against β-amyloid-induced toxicity by attenuating tau phosphorylation. Eur J Neurosci 28:1989–2002
    • (2008) Eur J Neurosci , vol.28 , pp. 1989-2002
    • Song, M.S.1    Rauw, G.2    Baker, G.B.3    Kar, S.4
  • 59
    • 0345872128 scopus 로고    scopus 로고
    • Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial
    • COI: 1:CAS:528:DC%2BD2cXmtlantA%3D%3D, PID: 14734594
    • Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, Memantine study group (2004) Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 291:317–324
    • (2004) JAMA , vol.291 , pp. 317-324
    • Tariot, P.N.1    Farlow, M.R.2    Grossberg, G.T.3    Graham, S.M.4    McDonald, S.5    Gergel, I.6    Memantine study group7
  • 60
    • 52649127458 scopus 로고    scopus 로고
    • Long-term course and effectiveness of combination therapy in Alzheimer disease
    • COI: 1:CAS:528:DC%2BD1cXhtVOiu7%2FE, PID: 18580597
    • Atri A, Shaughnessy LW, Locascio JJ, Growdon JH (2008) Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 22:209–221
    • (2008) Alzheimer Dis Assoc Disord , vol.22 , pp. 209-221
    • Atri, A.1    Shaughnessy, L.W.2    Locascio, J.J.3    Growdon, J.H.4
  • 61
    • 84858799331 scopus 로고    scopus 로고
    • 1-Benzyl-1,2,3,4-tetrahydro-carboline as channel blocker of N-methyl-d-aspartate receptors
    • COI: 1:CAS:528:DC%2BC38XltVajs7g%3D, PID: 22226015
    • Espinoza-Moraga M, Caballero J, Gaube F, Winckler T, Santos LS (2012) 1-Benzyl-1,2,3,4-tetrahydro-carboline as channel blocker of N-methyl-d-aspartate receptors. Chem Biol Drug Des 79:594–599
    • (2012) Chem Biol Drug Des , vol.79 , pp. 594-599
    • Espinoza-Moraga, M.1    Caballero, J.2    Gaube, F.3    Winckler, T.4    Santos, L.S.5
  • 62
    • 84892816620 scopus 로고    scopus 로고
    • Synthesis, modeling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors
    • COI: 1:CAS:528:DC%2BC2cXlt1Gltg%3D%3D, PID: 24411196
    • Gitto R, De Luca L, Ferro S, Ruso E, Sarro GD, Chisari M et al (2014) Synthesis, modeling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors. Bioorg Med Chem 22:1040–1048
    • (2014) Bioorg Med Chem , vol.22 , pp. 1040-1048
    • Gitto, R.1    De Luca, L.2    Ferro, S.3    Ruso, E.4    Sarro, G.D.5    Chisari, M.6
  • 63
    • 70350455062 scopus 로고    scopus 로고
    • The beta-secretase enzyme BACE in health and Alzheimer’s disease: regulation, cell biology, function, and therapeutic potential
    • COI: 1:CAS:528:DC%2BD1MXhtlSit7bP, PID: 19828790
    • Vassar R, Kovacs DM, Yan R, Wong PC (2009) The beta-secretase enzyme BACE in health and Alzheimer’s disease: regulation, cell biology, function, and therapeutic potential. J Neurosci 29:12787–12794
    • (2009) J Neurosci , vol.29 , pp. 12787-12794
    • Vassar, R.1    Kovacs, D.M.2    Yan, R.3    Wong, P.C.4
  • 64
    • 17344388652 scopus 로고    scopus 로고
    • BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer’s disease therapeutics
    • COI: 1:CAS:528:DC%2BD3MXkslSrurs%3D, PID: 11406613
    • Roberds SL, Anderson J, Basi G, Bienkowski MJ, Branstetter DG, Chen KS et al (2001) BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer’s disease therapeutics. Hum Mol Genet 10:1317–1324
    • (2001) Hum Mol Genet , vol.10 , pp. 1317-1324
    • Roberds, S.L.1    Anderson, J.2    Basi, G.3    Bienkowski, M.J.4    Branstetter, D.G.5    Chen, K.S.6
  • 65
    • 0035116273 scopus 로고    scopus 로고
    • Mice deficient in BACE1, the Alzheimer’s beta-secretase, have normal phenotype and abolished beta-amyloid generation
    • COI: 1:CAS:528:DC%2BD3MXhsF2rtbY%3D, PID: 11224535
    • Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P et al (2001) Mice deficient in BACE1, the Alzheimer’s beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat Neurosci 4:231–232
    • (2001) Nat Neurosci , vol.4 , pp. 231-232
    • Luo, Y.1    Bolon, B.2    Kahn, S.3    Bennett, B.D.4    Babu-Khan, S.5    Denis, P.6
  • 66
    • 0034662929 scopus 로고    scopus 로고
    • BACE2, a beta- secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein
    • COI: 1:CAS:528:DC%2BD3cXmtVentL8%3D, PID: 10931940
    • Farzan M, Schnitzler CE, Vasilieva N, Leung D, Choe H (2000) BACE2, a beta- secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proc Natl Acad Sci USA 97:9712–9717
    • (2000) Proc Natl Acad Sci USA , vol.97 , pp. 9712-9717
    • Farzan, M.1    Schnitzler, C.E.2    Vasilieva, N.3    Leung, D.4    Choe, H.5
  • 67
    • 50649106648 scopus 로고    scopus 로고
    • Cathepsin D—many functions of one aspartic protease
    • PID: 18396408
    • Benes P, Vetvicka V, Fusek M (2008) Cathepsin D—many functions of one aspartic protease. Crit Rev Oncol Hematol 68:12–28
    • (2008) Crit Rev Oncol Hematol , vol.68 , pp. 12-28
    • Benes, P.1    Vetvicka, V.2    Fusek, M.3
  • 68
    • 0037085353 scopus 로고    scopus 로고
    • Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases
    • COI: 1:CAS:528:DC%2BD38XhsFeqtrc%3D, PID: 11741910
    • Gruninger-Leitch F, Schlatter D, Küng E, Nelböck P, Dobeli H (2002) Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases. J Biol Chem 277:4687–4693
    • (2002) J Biol Chem , vol.277 , pp. 4687-4693
    • Gruninger-Leitch, F.1    Schlatter, D.2    Küng, E.3    Nelböck, P.4    Dobeli, H.5
  • 69
    • 1942470549 scopus 로고    scopus 로고
    • Flap position of free memapsin 2 (beta-secretase), a model for flap opening in aspartic protease catalysis
    • COI: 1:CAS:528:DC%2BD2cXis1CjtL4%3D, PID: 15096037
    • Hong L, Tang J (2004) Flap position of free memapsin 2 (beta-secretase), a model for flap opening in aspartic protease catalysis. Biochemistry 43:4689–4695
    • (2004) Biochemistry , vol.43 , pp. 4689-4695
    • Hong, L.1    Tang, J.2
  • 70
    • 34250819839 scopus 로고    scopus 로고
    • Intracellular amyloid-beta in Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BD2sXmslWjsr8%3D
    • LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer’s disease. Nat Rev Neurosci 8:499–509
    • (2007) Nat Rev Neurosci , vol.8 , pp. 499-509
    • LaFerla, F.M.1    Green, K.N.2    Oddo, S.3
  • 71
    • 46749092486 scopus 로고    scopus 로고
    • Beta-secretase as a therapeutic target for Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BD1cXhtVOgtL3F, PID: 18625451
    • Ghosh AK, Gemma S, Tang J (2008) Beta-secretase as a therapeutic target for Alzheimer’s disease. Neurotherapeutics 5:399–408
    • (2008) Neurotherapeutics , vol.5 , pp. 399-408
    • Ghosh, A.K.1    Gemma, S.2    Tang, J.3
  • 72
    • 0035974650 scopus 로고    scopus 로고
    • Structure-based design: potent inhibitors of human brain memapsin 2 (beta-secretase)
    • COI: 1:CAS:528:DC%2BD3MXlsFygtbg%3D, PID: 11520194
    • Ghosh AK, Bilcer G, Harwood C, Kawahama R, Shin D, Hussain KA et al (2001) Structure-based design: potent inhibitors of human brain memapsin 2 (beta-secretase). J Med Chem 44:2865–2868
    • (2001) J Med Chem , vol.44 , pp. 2865-2868
    • Ghosh, A.K.1    Bilcer, G.2    Harwood, C.3    Kawahama, R.4    Shin, D.5    Hussain, K.A.6
  • 73
    • 42149166766 scopus 로고    scopus 로고
    • Memapsin 2 (beta-secretase) inhibitors: drug development
    • COI: 1:CAS:528:DC%2BD1cXkt1als7o%3D, PID: 18393797
    • Ghosh AK, Kumaragurubaran N, Hong L, Koelsh G, Tang J (2008) Memapsin 2 (beta-secretase) inhibitors: drug development. Curr Alzheimer Res 5:121–131
    • (2008) Curr Alzheimer Res , vol.5 , pp. 121-131
    • Ghosh, A.K.1    Kumaragurubaran, N.2    Hong, L.3    Koelsh, G.4    Tang, J.5
  • 78
    • 84983565966 scopus 로고    scopus 로고
    • Peptide derivatives having β-secretase inhibitory activity
    • Kiso Y (2007) Peptide derivatives having β-secretase inhibitory activity. US Patent US7312188, 2007
    • (2007) US Patent US7312188 , pp. 2007
    • Kiso, Y.1
  • 79
    • 9644266667 scopus 로고    scopus 로고
    • Design and synthesis of highly active Alzheimer’s beta-secretase (BACE1) inhibitors, KMI-420 And KMI-429, with enhanced chemical stability
    • COI: 1:CAS:528:DC%2BD2cXhtVKrsLnF, PID: 15582441
    • Kimura T, Shuto D, Hamada Y, Igawa N, Kasai S, Liu P et al (2005) Design and synthesis of highly active Alzheimer’s beta-secretase (BACE1) inhibitors, KMI-420 And KMI-429, with enhanced chemical stability. Bioorg Med Chem Lett 15:211–215
    • (2005) Bioorg Med Chem Lett , vol.15 , pp. 211-215
    • Kimura, T.1    Shuto, D.2    Hamada, Y.3    Igawa, N.4    Kasai, S.5    Liu, P.6
  • 80
    • 78650741819 scopus 로고    scopus 로고
    • Investigation of α-phenylnorstatine and α-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors
    • COI: 1:CAS:528:DC%2BC3MXhs1WktA%3D%3D, PID: 21183353
    • Wangsell F, Nordeman P, Sävmarker J, Emanuelsson R, Jansson K, Lindberg J et al (2011) Investigation of α-phenylnorstatine and α-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors. Bioorg Med Chem 19:145–155
    • (2011) Bioorg Med Chem , vol.19 , pp. 145-155
    • Wangsell, F.1    Nordeman, P.2    Sävmarker, J.3    Emanuelsson, R.4    Jansson, K.5    Lindberg, J.6
  • 81
  • 82
    • 38149128145 scopus 로고    scopus 로고
    • Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1′ substrate binding pocket
    • COI: 1:CAS:528:DC%2BD1cXosFWrsQ%3D%3D, PID: 18068983
    • Jennings LD, Cole DC, Stock JR, Sukhdeo MN, Ellingboe JW, Cowling R et al (2008) Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1′ substrate binding pocket. Bioorg Med Chem Lett 18:767–771
    • (2008) Bioorg Med Chem Lett , vol.18 , pp. 767-771
    • Jennings, L.D.1    Cole, D.C.2    Stock, J.R.3    Sukhdeo, M.N.4    Ellingboe, J.W.5    Cowling, R.6
  • 83
    • 38749095202 scopus 로고    scopus 로고
    • Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets
    • COI: 1:CAS:528:DC%2BD1cXhsFWlt7w%3D, PID: 18162398
    • Cole DC, Stock JR, Chopra R, Cowling R, Ellingboe JW, Fan KY et al (2008) Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets. Bioorg Med Chem Lett 18:1063–1066
    • (2008) Bioorg Med Chem Lett , vol.18 , pp. 1063-1066
    • Cole, D.C.1    Stock, J.R.2    Chopra, R.3    Cowling, R.4    Ellingboe, J.W.5    Fan, K.Y.6
  • 84
    • 33947636525 scopus 로고    scopus 로고
    • Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase
    • COI: 1:CAS:528:DC%2BD2sXhvFags7s%3D, PID: 17315857
    • Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA et al (2007) Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase. J Med Chem 50:1124–1132
    • (2007) J Med Chem , vol.50 , pp. 1124-1132
    • Congreve, M.1    Aharony, D.2    Albert, J.3    Callaghan, O.4    Campbell, J.5    Carr, R.A.6
  • 85
    • 77949659631 scopus 로고    scopus 로고
    • Novel pyrrolyl 2-aminopyridines as potent and selective human beta-secretase (BACE1) inhibitors
    • COI: 1:CAS:528:DC%2BC3cXjslGmsLw%3D, PID: 20223661
    • Malamas MS, Barnes K, Hui Y, Johnson M, Lovering F, Condon J et al (2010) Novel pyrrolyl 2-aminopyridines as potent and selective human beta-secretase (BACE1) inhibitors. Bioorg Med Chem Lett 20:2068–2073
    • (2010) Bioorg Med Chem Lett , vol.20 , pp. 2068-2073
    • Malamas, M.S.1    Barnes, K.2    Hui, Y.3    Johnson, M.4    Lovering, F.5    Condon, J.6
  • 87
    • 84855983969 scopus 로고    scopus 로고
    • A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: structure-based design, synthesis, and biological evaluation
    • COI: 1:CAS:528:DC%2BC38XhtFKmt7w%3D, PID: 22209418
    • Chiriano G, De Simone A, Mancini F, Perez DI, Cavalli A, Bolognesi ML et al (2012) A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: structure-based design, synthesis, and biological evaluation. Eur J Med Chem 48:206–213
    • (2012) Eur J Med Chem , vol.48 , pp. 206-213
    • Chiriano, G.1    De Simone, A.2    Mancini, F.3    Perez, D.I.4    Cavalli, A.5    Bolognesi, M.L.6
  • 88
    • 70350050829 scopus 로고    scopus 로고
    • Aminoimidazoles as potent and selective human beta-secretase (BACE1) inhibitors
    • COI: 1:CAS:528:DC%2BD1MXhtFCjtrvM, PID: 19757823
    • Malamas MS, Erdei J, Gunawan I, Barnes K, Johnson M, Hui Y et al (2009) Aminoimidazoles as potent and selective human beta-secretase (BACE1) inhibitors. J Med Chem 52:6314–6323
    • (2009) J Med Chem , vol.52 , pp. 6314-6323
    • Malamas, M.S.1    Erdei, J.2    Gunawan, I.3    Barnes, K.4    Johnson, M.5    Hui, Y.6
  • 89
    • 84655164337 scopus 로고    scopus 로고
    • Discovery of pyrrolidine-based β-secretase inhibitors: lead advancement through conformational design for maintenance of ligand binding efficiency
    • COI: 1:CAS:528:DC%2BC38XivVyjtw%3D%3D, PID: 22130130
    • Stachel SJ, Steele TG, Petrocchi A, Haugabook SJ, McGaughey G, Katharine Holloway M et al (2012) Discovery of pyrrolidine-based β-secretase inhibitors: lead advancement through conformational design for maintenance of ligand binding efficiency. Bioorg Med Chem Lett 22:240–244
    • (2012) Bioorg Med Chem Lett , vol.22 , pp. 240-244
    • Stachel, S.J.1    Steele, T.G.2    Petrocchi, A.3    Haugabook, S.J.4    McGaughey, G.5    Katharine Holloway, M.6
  • 90
    • 65149086462 scopus 로고    scopus 로고
    • Discovery of aminoheterocycles as a novel beta-secretase inhibitor class: pH dependence on binding activity part 1
    • COI: 1:CAS:528:DC%2BD1MXmtVeku7s%3D, PID: 19409780
    • Stachel SJ, Coburn CA, Rush D, Jones KL, Zhu H, Rajapakse H et al (2009) Discovery of aminoheterocycles as a novel beta-secretase inhibitor class: pH dependence on binding activity part 1. Bioorg Med Chem Lett 19:2977–2980
    • (2009) Bioorg Med Chem Lett , vol.19 , pp. 2977-2980
    • Stachel, S.J.1    Coburn, C.A.2    Rush, D.3    Jones, K.L.4    Zhu, H.5    Rajapakse, H.6
  • 91
    • 84878095153 scopus 로고    scopus 로고
    • β-Secretase (BACE1) inhibitors with high in vivo efficacy suitable for clinical evaluation in Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BC3sXmtVymuro%3D, PID: 23590342
    • Hilpert H, Guba W, Woltering TJ, Wostl W, Pinard E, Mauser H et al (2013) β-Secretase (BACE1) inhibitors with high in vivo efficacy suitable for clinical evaluation in Alzheimer’s disease. J Med Chem 56:3980–3995
    • (2013) J Med Chem , vol.56 , pp. 3980-3995
    • Hilpert, H.1    Guba, W.2    Woltering, T.J.3    Wostl, W.4    Pinard, E.5    Mauser, H.6
  • 92
    • 77957880162 scopus 로고    scopus 로고
    • Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors
    • COI: 1:CAS:528:DC%2BC3cXht1KrsbvL, PID: 20850315
    • Xu W, Chen G, Zhu W, Zuo Z (2010) Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors. Bioorg Med Chem Lett 20:6203–6207
    • (2010) Bioorg Med Chem Lett , vol.20 , pp. 6203-6207
    • Xu, W.1    Chen, G.2    Zhu, W.3    Zuo, Z.4
  • 93
    • 0242285619 scopus 로고    scopus 로고
    • Green tea catechins as a BACE1 (beta-secretase) inhibitor
    • COI: 1:CAS:528:DC%2BD3sXosVWrsrs%3D, PID: 14592472
    • Jeon SY, Bae K, Seong YH, Song KS (2003) Green tea catechins as a BACE1 (beta-secretase) inhibitor. Bioorg Med Chem Lett 13:3905–3908
    • (2003) Bioorg Med Chem Lett , vol.13 , pp. 3905-3908
    • Jeon, S.Y.1    Bae, K.2    Seong, Y.H.3    Song, K.S.4
  • 94
    • 34249307258 scopus 로고    scopus 로고
    • Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax rhizoma
    • COI: 1:CAS:528:DC%2BD2sXosF2ht74%3D, PID: 17084604
    • Jeon SY, Kwon SH, Seong YH, Bae K, Hur JM, Lee YY et al (2007) Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax rhizoma. Phytomedicine 14:403–408
    • (2007) Phytomedicine , vol.14 , pp. 403-408
    • Jeon, S.Y.1    Kwon, S.H.2    Seong, Y.H.3    Bae, K.4    Hur, J.M.5    Lee, Y.Y.6
  • 95
    • 77951618523 scopus 로고    scopus 로고
    • β-secretase inhibitory effects of furanocoumarins from the root of Angelica dahurica
    • COI: 1:CAS:528:DC%2BC3cXlvVKju7k%3D, PID: 20041416
    • Marumoto S, Miyazawa M (2010) β-secretase inhibitory effects of furanocoumarins from the root of Angelica dahurica. Phytother Res 24:510–513
    • (2010) Phytother Res , vol.24 , pp. 510-513
    • Marumoto, S.1    Miyazawa, M.2
  • 96
    • 84855775879 scopus 로고    scopus 로고
    • Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor
    • COI: 1:CAS:528:DC%2BC38XpsFSnug%3D%3D, PID: 22222157
    • Marumoto S, Miyazawa M (2012) Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor. Bioorg Med Chem 20:784–788
    • (2012) Bioorg Med Chem , vol.20 , pp. 784-788
    • Marumoto, S.1    Miyazawa, M.2
  • 97
    • 45049086920 scopus 로고    scopus 로고
    • Flavonols and flavones as BACE-1 inhibitors: structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features
    • COI: 1:CAS:528:DC%2BD1cXkvFWqurw%3D, PID: 18295609
    • Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H (2008) Flavonols and flavones as BACE-1 inhibitors: structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta 1780:819–825
    • (2008) Biochim Biophys Acta , vol.1780 , pp. 819-825
    • Shimmyo, Y.1    Kihara, T.2    Akaike, A.3    Niidome, T.4    Sugimoto, H.5
  • 98
    • 79955561984 scopus 로고    scopus 로고
    • Inhibition and structural reliability of prenylated flavones from the stem bark of Morus ihou on β-secretase (BACE-1)
    • COI: 1:CAS:528:DC%2BC3MXlsVCmtb4%3D, PID: 21511472
    • Cho JK, Ryu YB, Curtis-Long MJ, Kim JY, Kim D, Lee S et al (2011) Inhibition and structural reliability of prenylated flavones from the stem bark of Morus ihou on β-secretase (BACE-1). Bioorg Med Chem Lett 21:2945–2948
    • (2011) Bioorg Med Chem Lett , vol.21 , pp. 2945-2948
    • Cho, J.K.1    Ryu, Y.B.2    Curtis-Long, M.J.3    Kim, J.Y.4    Kim, D.5    Lee, S.6
  • 99
    • 84870857669 scopus 로고    scopus 로고
    • BACE inhibitory flavanones from Balanophora involucrata Hook. f
    • COI: 1:CAS:528:DC%2BC38XhsFWjsLrL, PID: 22909424
    • Tao J, Zhao J, Zhao Y, Cui Y, Fang W (2012) BACE inhibitory flavanones from Balanophora involucrata Hook. f. Fitoterapia 83:1386–1390
    • (2012) Fitoterapia , vol.83 , pp. 1386-1390
    • Tao, J.1    Zhao, J.2    Zhao, Y.3    Cui, Y.4    Fang, W.5
  • 100
    • 77953290521 scopus 로고    scopus 로고
    • Molecular docking studies of phlorotannins from Eisenia bicyclis with BACE1 inhibitory activity
    • COI: 1:CAS:528:DC%2BC3cXmsVOhtr8%3D, PID: 20462757
    • Jung HA, Oh SH, Choi JS (2010) Molecular docking studies of phlorotannins from Eisenia bicyclis with BACE1 inhibitory activity. Bioorg Med Chem Lett 20:3211–3215
    • (2010) Bioorg Med Chem Lett , vol.20 , pp. 3211-3215
    • Jung, H.A.1    Oh, S.H.2    Choi, J.S.3
  • 101
    • 84983566008 scopus 로고    scopus 로고
    • Alzforum. Therapeutics LY2886721. http://www.alzforum.org/therapeutics/ly2886721. Accessed 11 Jan 2016
  • 102
    • 84983561409 scopus 로고    scopus 로고
    • Alzforum. Accessed 11 Jan
    • Alzforum. Therapeutics Verubecestat. http://www.alzforum.org/therapeutics/verubecestat. Accessed 11 Jan 2016
    • (2016) Therapeutics Verubecestat
  • 107
    • 84983522694 scopus 로고    scopus 로고
    • Alzforum. Accessed 11 Jan
    • Alzforum. Therapeutics E2609. http://www.alzforum.org/therapeutics/E2609. Accessed 11 Jan 2016
    • (2016) Therapeutics E2609
  • 108
    • 84880712325 scopus 로고    scopus 로고
    • A phase 3 trial of semagacestat for treatment of Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BC3sXhtF2nur7L, PID: 23883379
    • Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S et al (2013) A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med 369:341–350
    • (2013) N Engl J Med , vol.369 , pp. 341-350
    • Doody, R.S.1    Raman, R.2    Farlow, M.3    Iwatsubo, T.4    Vellas, B.5    Joffe, S.6
  • 109
    • 84866411763 scopus 로고    scopus 로고
    • BMS-708,163 targets presenilin and lacks notch-sparing activity
    • COI: 1:CAS:528:DC%2BC38Xht1ymsrzL, PID: 22931393
    • Crump CJ, Castro SV, Wang F, Pozdnyakov N, Ballard TE, Sisodia SS et al (2012) BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry 51:7209–7211
    • (2012) Biochemistry , vol.51 , pp. 7209-7211
    • Crump, C.J.1    Castro, S.V.2    Wang, F.3    Pozdnyakov, N.4    Ballard, T.E.5    Sisodia, S.S.6
  • 110
    • 84983478668 scopus 로고    scopus 로고
    • EU Clinical Trials Register. Accessed 28 Jan
    • EU Clinical Trials Register. Clinical trials for BMS-708163. https://www.clinicaltrialsregister.eu/ctr-search/search?query=BMS-708163. Accessed 28 Jan 2016
    • (2016) Clinical trials for BMS-708163
  • 112
    • 84868516038 scopus 로고    scopus 로고
    • Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease
    • PID: 22892585
    • Coric V, Van Dyck CH, Salloway S, Andreasen N, Brody M, Richter RW et al (2012) Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol 69:1430–1440
    • (2012) Arch Neurol , vol.69 , pp. 1430-1440
    • Coric, V.1    Van Dyck, C.H.2    Salloway, S.3    Andreasen, N.4    Brody, M.5    Richter, R.W.6
  • 113
    • 84946709627 scopus 로고    scopus 로고
    • Targeting prodromal Alzheimer’s disease with avagacestat: a randomized clinical trial
    • Coric V, Salloway S, Van Dyck CH, Dubois B, Andreasen N, Brody M et al (2015) Targeting prodromal Alzheimer’s disease with avagacestat: a randomized clinical trial. JAMA Neurol 28:1–10
    • (2015) JAMA Neurol , vol.28 , pp. 1-10
    • Coric, V.1    Salloway, S.2    Van Dyck, C.H.3    Dubois, B.4    Andreasen, N.5    Brody, M.6
  • 115
    • 0038719688 scopus 로고    scopus 로고
    • Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces abeta 42 generation
    • COI: 1:CAS:528:DC%2BD3sXjs1KhtLY%3D, PID: 12637581
    • Takahashi Y, Hayashi I, Tominari Y, Rikimaru K, Morohashi Y, Kan T et al (2003) Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces abeta 42 generation. J Biol Chem 278:18664–18670
    • (2003) J Biol Chem , vol.278 , pp. 18664-18670
    • Takahashi, Y.1    Hayashi, I.2    Tominari, Y.3    Rikimaru, K.4    Morohashi, Y.5    Kan, T.6
  • 116
    • 0042904882 scopus 로고    scopus 로고
    • Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) And ErbB-4 receptor and signaling through the APP intracellular domain
    • COI: 1:CAS:528:DC%2BD3sXmtFeqsLk%3D, PID: 12777371
    • Weggen S, Eriksen JL, Sagi SA, Pietrzik CU, Golde TE, Koo EH (2003) Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) And ErbB-4 receptor and signaling through the APP intracellular domain. J Biol Chem 278:30748–30754
    • (2003) J Biol Chem , vol.278 , pp. 30748-30754
    • Weggen, S.1    Eriksen, J.L.2    Sagi, S.A.3    Pietrzik, C.U.4    Golde, T.E.5    Koo, E.H.6
  • 117
    • 40349106236 scopus 로고    scopus 로고
    • Gamma-secretase modulation and its promise for Alzheimer’s disease: a medicinal chemistry perspective
    • COI: 1:CAS:528:DC%2BD1cXhtlWnt74%3D, PID: 18220931
    • Peretto I, La Porta E (2008) Gamma-secretase modulation and its promise for Alzheimer’s disease: a medicinal chemistry perspective. Curr Top Med Chem 8:38–46
    • (2008) Curr Top Med Chem , vol.8 , pp. 38-46
    • Peretto, I.1    La Porta, E.2
  • 118
    • 37349104196 scopus 로고    scopus 로고
    • Safety, tolerability, pharmacokinetics, and Aβ levels after short-term administration of R-flurbiprofen in healthy elderly individuals
    • COI: 1:CAS:528:DC%2BD1cXjsValsQ%3D%3D, PID: 18090435
    • Galasko D, Graff-Radford N, May S, Hendrix S, Cottrell B, Sagi S et al (2007) Safety, tolerability, pharmacokinetics, and Aβ levels after short-term administration of R-flurbiprofen in healthy elderly individuals. Alzheimer Dis Assoc Disord 21:292–299
    • (2007) Alzheimer Dis Assoc Disord , vol.21 , pp. 292-299
    • Galasko, D.1    Graff-Radford, N.2    May, S.3    Hendrix, S.4    Cottrell, B.5    Sagi, S.6
  • 119
    • 33845931855 scopus 로고    scopus 로고
    • Scaffold of the cyclooxygenase-2 (cox-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators
    • COI: 1:CAS:528:DC%2BD28XhtlCqsLvL, PID: 17181139
    • Narlawar R, Pérez Revuelta BI, Haass C, Steiner H, Schmidt B, Baumann K (2006) Scaffold of the cyclooxygenase-2 (cox-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators. J Med Chem 49:7588–7591
    • (2006) J Med Chem , vol.49 , pp. 7588-7591
    • Narlawar, R.1    Pérez Revuelta, B.I.2    Haass, C.3    Steiner, H.4    Schmidt, B.5    Baumann, K.6
  • 121
    • 74049093168 scopus 로고    scopus 로고
    • Piperazinyl pyrimidine derivatives as potent gamma-secretase modulators
    • COI: 1:CAS:528:DC%2BC3cXhtVGrtLY%3D, PID: 20022243
    • Rivkin A, Ahearn SP, Chichetti SM, Kim YR, Li C, Rosenau A et al (2010) Piperazinyl pyrimidine derivatives as potent gamma-secretase modulators. Bioorg Med Chem Lett 20:1269–1271
    • (2010) Bioorg Med Chem Lett , vol.20 , pp. 1269-1271
    • Rivkin, A.1    Ahearn, S.P.2    Chichetti, S.M.3    Kim, Y.R.4    Li, C.5    Rosenau, A.6
  • 123
    • 84868690878 scopus 로고    scopus 로고
    • Discovery of a novel pharmacological and structural class of gamma secretase modulators derived from the extract of Actaea Racemosa
    • COI: 1:CAS:528:DC%2BC38Xht1Kms77I, PID: 23205187
    • Findeis MA, Schroeder F, McKee TD, Yager D, Fraering PC, Creaser SP et al (2012) Discovery of a novel pharmacological and structural class of gamma secretase modulators derived from the extract of Actaea Racemosa. ACS Chem Neurosci 3:941–951
    • (2012) ACS Chem Neurosci , vol.3 , pp. 941-951
    • Findeis, M.A.1    Schroeder, F.2    McKee, T.D.3    Yager, D.4    Fraering, P.C.5    Creaser, S.P.6
  • 124
    • 0029841562 scopus 로고    scopus 로고
    • Increased activity-regulating and neuroprotective efficacy of alpha-secretase derived secreted amyloid precursor protein conferred by a C-terminal heparin binding domain
    • COI: 1:CAS:528:DyaK28XmsV2rtr0%3D, PID: 8863493
    • Furukawa K, Sopher B, Rydel R, Begley J, Pham D, Martin G et al (1996) Increased activity-regulating and neuroprotective efficacy of alpha-secretase derived secreted amyloid precursor protein conferred by a C-terminal heparin binding domain. J Neurochem 67:1882–1896
    • (1996) J Neurochem , vol.67 , pp. 1882-1896
    • Furukawa, K.1    Sopher, B.2    Rydel, R.3    Begley, J.4    Pham, D.5    Martin, G.6
  • 125
    • 0028213567 scopus 로고
    • A heparin-binding domain in the amyloid protein precursor of Alzheimer’s disease is involved in the regulation of neurite outgrowth
    • COI: 1:CAS:528:DyaK2cXktVKju70%3D, PID: 8158260
    • Small D, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K et al (1994) A heparin-binding domain in the amyloid protein precursor of Alzheimer’s disease is involved in the regulation of neurite outgrowth. J Neurosci 14:2117–2127
    • (1994) J Neurosci , vol.14 , pp. 2117-2127
    • Small, D.1    Nurcombe, V.2    Reed, G.3    Clarris, H.4    Moir, R.5    Beyreuther, K.6
  • 126
    • 0033616716 scopus 로고    scopus 로고
    • Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease
    • COI: 1:CAS:528:DyaK1MXjslChsLY%3D, PID: 10097139
    • Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M et al (1999) Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 96:3922–3927
    • (1999) Proc Natl Acad Sci USA , vol.96 , pp. 3922-3927
    • Lammich, S.1    Kojro, E.2    Postina, R.3    Gilbert, S.4    Pfeiffer, R.5    Jasionowski, M.6
  • 127
    • 33750991103 scopus 로고    scopus 로고
    • Overexpression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice
    • COI: 1:CAS:528:DC%2BD28Xht1ersr%2FM, PID: 17014917
    • Schmitt U, Hiemke C, Fahrenholz F, Schroeder A (2006) Overexpression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice. Behav Brain Res 175:278–284
    • (2006) Behav Brain Res , vol.175 , pp. 278-284
    • Schmitt, U.1    Hiemke, C.2    Fahrenholz, F.3    Schroeder, A.4
  • 128
    • 39749142725 scopus 로고    scopus 로고
    • ADAM-10 over-expression increases cortical synaptogenesis
    • COI: 1:CAS:528:DC%2BD1cXjtVersr8%3D, PID: 17187903
    • Bell KFS, Zheng L, Fahrenholz F, Cuello AC (2008) ADAM-10 over-expression increases cortical synaptogenesis. Neurobiol Aging 29:554–565
    • (2008) Neurobiol Aging , vol.29 , pp. 554-565
    • Bell, K.F.S.1    Zheng, L.2    Fahrenholz, F.3    Cuello, A.C.4
  • 129
    • 0026476297 scopus 로고
    • Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors
    • COI: 1:CAS:528:DyaK38XmtlWmtrw%3D, PID: 1411529
    • Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258:304–307
    • (1992) Science , vol.258 , pp. 304-307
    • Nitsch, R.M.1    Slack, B.E.2    Wurtman, R.J.3    Growdon, J.H.4
  • 130
    • 0035977026 scopus 로고    scopus 로고
    • The human serotonin 5-HT4 receptor regulates secretion of nonamyloidogenic precursor protein
    • COI: 1:CAS:528:DC%2BD3MXovFegurk%3D, PID: 11584021
    • Robert S, Zugaza J, Fischmeister R, Gardier A, Lezoualc’h F (2001) The human serotonin 5-HT4 receptor regulates secretion of nonamyloidogenic precursor protein. J Biol Chem 276:44881–44888
    • (2001) J Biol Chem , vol.276 , pp. 44881-44888
    • Robert, S.1    Zugaza, J.2    Fischmeister, R.3    Gardier, A.4    Lezoualc’h, F.5
  • 131
    • 84873360340 scopus 로고    scopus 로고
    • Etazolate, an α-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice
    • COI: 1:CAS:528:DC%2BC3sXhs1Cms74%3D, PID: 23178198
    • Siopi E, Llufriu-Daben G, Cho AH, Vidal-Lletjos S, Plotkine M, Marchand-Leroux C et al (2013) Etazolate, an α-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice. Neuropharmacology 67:183–192
    • (2013) Neuropharmacology , vol.67 , pp. 183-192
    • Siopi, E.1    Llufriu-Daben, G.2    Cho, A.H.3    Vidal-Lletjos, S.4    Plotkine, M.5    Marchand-Leroux, C.6
  • 132
    • 0034820554 scopus 로고    scopus 로고
    • Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy
    • COI: 1:CAS:528:DC%2BD3MXnvVCltL0%3D, PID: 11676287
    • Gervais F, Chalifour R, Garceau D, Kong X, Laurin J, Mclaughlin R et al (2001) Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy. Amyloid 8:28–35
    • (2001) Amyloid , vol.8 , pp. 28-35
    • Gervais, F.1    Chalifour, R.2    Garceau, D.3    Kong, X.4    Laurin, J.5    Mclaughlin, R.6
  • 133
    • 33847133125 scopus 로고    scopus 로고
    • Targeting soluble Aβ peptide with tramiprosate for the treatment of brain amyloidosis
    • COI: 1:CAS:528:DC%2BD2sXitFyks74%3D, PID: 16675063
    • Gervais F, Paquette J, Morissette C, Krzywkowski P, Yu M, Azzi M et al (2007) Targeting soluble Aβ peptide with tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 28:537–547
    • (2007) Neurobiol Aging , vol.28 , pp. 537-547
    • Gervais, F.1    Paquette, J.2    Morissette, C.3    Krzywkowski, P.4    Yu, M.5    Azzi, M.6
  • 134
    • 77951776829 scopus 로고    scopus 로고
    • Alzheimer’s disease: strategies for disease modification
    • Citron M (2004) Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov 9:387–398
    • (2004) Nat Rev Drug Discov , vol.9 , pp. 387-398
    • Citron, M.1
  • 135
    • 33845388059 scopus 로고    scopus 로고
    • A phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease
    • COI: 1:CAS:528:DC%2BD28Xht1SjsLzN, PID: 17082468
    • Aisen P, Saumier D, Briand R, Laurin J, Gervais F, Tremblay P et al (2006) A phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology 67:1757–1763
    • (2006) Neurology , vol.67 , pp. 1757-1763
    • Aisen, P.1    Saumier, D.2    Briand, R.3    Laurin, J.4    Gervais, F.5    Tremblay, P.6
  • 136
    • 84983476872 scopus 로고    scopus 로고
    • Transition Therapeutics Announces Results of Data Analysis from ELND005 Phase 2/3 Clinical Study in Agitation and Aggression in Alzheimer’s Disease Patients. Accessed 9 Feb 2016
    • Transition Therapeutics Announces Results of Data Analysis from ELND005 Phase 2/3 Clinical Study in Agitation and Aggression in Alzheimer’s Disease Patients. http://www.prnewswire.com/news-releases/transition-therapeutics-announces-results-of-data-analysis-from-elnd005-phase-23-clinical-study-in-agitation-and-aggression-in-alzheimers-disease-patients-533007951.html. Accessed 9 Feb 2016
  • 137
    • 84897018530 scopus 로고    scopus 로고
    • A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BC2cXptVGksQ%3D%3D, PID: 24102330
    • Hoshino A, Helwig M, Rezaei S, Berridge C, Eriksen JL, Lindberg I (2014) A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer’s disease. J Neurochem 128:419–430
    • (2014) J Neurochem , vol.128 , pp. 419-430
    • Hoshino, A.1    Helwig, M.2    Rezaei, S.3    Berridge, C.4    Eriksen, J.L.5    Lindberg, I.6
  • 138
    • 0036240395 scopus 로고    scopus 로고
    • Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model
    • COI: 1:CAS:528:DC%2BD38XjtFykurY%3D, PID: 11941374
    • Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C et al (2002) Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model. Nat Neurosci 5:452–457
    • (2002) Nat Neurosci , vol.5 , pp. 452-457
    • Dodart, J.C.1    Bales, K.R.2    Gannon, K.S.3    Greene, S.J.4    DeMattos, R.B.5    Mathis, C.6
  • 139
    • 20944448555 scopus 로고    scopus 로고
    • Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial
    • COI: 1:CAS:528:DC%2BD2MXjsVCjsbg%3D, PID: 15883316
    • Gilman S, Koller M, Black R, Jenkins L, Griffith S, Fox N et al (2005) Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64:1553–1562
    • (2005) Neurology , vol.64 , pp. 1553-1562
    • Gilman, S.1    Koller, M.2    Black, R.3    Jenkins, L.4    Griffith, S.5    Fox, N.6
  • 140
    • 47949132196 scopus 로고    scopus 로고
    • Active and passive immunotherapy for neurodegenerative disorders
    • COI: 1:CAS:528:DC%2BD1cXpt12nsrs%3D, PID: 18352830
    • Brody D, Holtzman D (2008) Active and passive immunotherapy for neurodegenerative disorders. Annu Rev Neurosci 31:175–193
    • (2008) Annu Rev Neurosci , vol.31 , pp. 175-193
    • Brody, D.1    Holtzman, D.2
  • 141
    • 10744230547 scopus 로고    scopus 로고
    • Sub acute meningoencephalitis in a subset of patients with AD after Abeta42 immunization
    • COI: 1:CAS:528:DC%2BD3sXks1OktLk%3D, PID: 12847155
    • Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC et al (2003) Sub acute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 61:46–54
    • (2003) Neurology , vol.61 , pp. 46-54
    • Orgogozo, J.M.1    Gilman, S.2    Dartigues, J.F.3    Laurent, B.4    Puel, M.5    Kirby, L.C.6
  • 143
    • 73349091534 scopus 로고    scopus 로고
    • A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
    • COI: 1:CAS:528:DC%2BD1MXhsFait7rN, PID: 19923550
    • Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M et al (2009) A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 73:2061–2070
    • (2009) Neurology , vol.73 , pp. 2061-2070
    • Salloway, S.1    Sperling, R.2    Gilman, S.3    Fox, N.C.4    Blennow, K.5    Raskind, M.6
  • 144
    • 84983515249 scopus 로고    scopus 로고
    • Alzforum. Accessed 12 Feb
    • Alzforum. Therapeutics Rember TM. http://www.alzforum.org/therapeutics/rember-tm. Accessed 12 Feb 2016
    • (2016) Therapeutics Rember TM
  • 145
    • 84862281225 scopus 로고    scopus 로고
    • Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo
    • COI: 1:CAS:528:DC%2BC38Xht1art73N, PID: 22361619
    • Congdon EE, Wu JW, Myeku N, Figueroa YH, Herman M, Marinec PS et al (2012) Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy 8:609–622
    • (2012) Autophagy , vol.8 , pp. 609-622
    • Congdon, E.E.1    Wu, J.W.2    Myeku, N.3    Figueroa, Y.H.4    Herman, M.5    Marinec, P.S.6
  • 146
    • 84876588286 scopus 로고    scopus 로고
    • Aminothienopyridazines and methylene blue affect tau fibrillization via cysteine oxidation
    • COI: 1:CAS:528:DC%2BC3sXmt12gtbY%3D, PID: 23443659
    • Crowe A, James MJ, Lee VM, Smith AB 3rd, Trojanowski JQ, Ballatore C et al (2013) Aminothienopyridazines and methylene blue affect tau fibrillization via cysteine oxidation. J Biol Chem 288:11024–11037
    • (2013) J Biol Chem , vol.288 , pp. 11024-11037
    • Crowe, A.1    James, M.J.2    Lee, V.M.3    Smith, A.B.4    Trojanowski, J.Q.5    Ballatore, C.6
  • 147
    • 84921531217 scopus 로고    scopus 로고
    • Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BC2MXhslensbw%3D, PID: 25550228
    • Wischik CM, Staff RT, Wischik DJ, Bentham P, Murray AD, Storey JM et al (2015) Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer’s disease. J Alzheimers Dis 44:705–720
    • (2015) J Alzheimers Dis , vol.44 , pp. 705-720
    • Wischik, C.M.1    Staff, R.T.2    Wischik, D.J.3    Bentham, P.4    Murray, A.D.5    Storey, J.M.6
  • 148
    • 84983561456 scopus 로고    scopus 로고
    • Adis Insight. Accessed 16 Feb
    • Adis Insight. Drug Profile TRx 0237. http://adisinsight.springer.com/drugs/800034429. Accessed 16 Feb 2016
    • (2016) Drug Profile TRx 0237
  • 149
    • 84983561464 scopus 로고    scopus 로고
    • TauRx Therapeutics. Accessed 16 Feb 2016
    • TauRx Therapeutics. http://taurx.com/taurx-005-enrolment.html. Accessed 16 Feb 2016
  • 150
    • 34548299424 scopus 로고    scopus 로고
    • Developing pharmacological therapies for Alzheimer disease
    • COI: 1:CAS:528:DC%2BD2sXhtFygtr3I, PID: 17604997
    • Iqbal K, Grundke-Iqbal I (2007) Developing pharmacological therapies for Alzheimer disease. Cell Mol Life Sci 64:2234–2244
    • (2007) Cell Mol Life Sci , vol.64 , pp. 2234-2244
    • Iqbal, K.1    Grundke-Iqbal, I.2
  • 151
    • 33845530335 scopus 로고    scopus 로고
    • Chronic lithium administration to FTDP-17 tau and GSK-3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert
    • COI: 1:CAS:528:DC%2BD2sXjsFGkug%3D%3D, PID: 17059563
    • Engel T, Goni-Oliver P, Lucas JJ, Avila J, Hernandez F (2006) Chronic lithium administration to FTDP-17 tau and GSK-3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert. J Neurochem 99:1445–1455
    • (2006) J Neurochem , vol.99 , pp. 1445-1455
    • Engel, T.1    Goni-Oliver, P.2    Lucas, J.J.3    Avila, J.4    Hernandez, F.5
  • 152
    • 33646922314 scopus 로고    scopus 로고
    • Full reversal of Alzheimer’s disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3
    • COI: 1:CAS:528:DC%2BD28Xlt1CjurY%3D, PID: 16687499
    • Engel T, Hernandez F, Avila J, Lucas JJ (2006) Full reversal of Alzheimer’s disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3. J Neurosci 26:5083–5090
    • (2006) J Neurosci , vol.26 , pp. 5083-5090
    • Engel, T.1    Hernandez, F.2    Avila, J.3    Lucas, J.J.4
  • 153
    • 0242720372 scopus 로고    scopus 로고
    • Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model
    • COI: 1:CAS:528:DC%2BD3sXos1Cls7s%3D, PID: 14624025
    • Perez M, Hernandez F, Lim F, Díaz-Nido J, Avila J (2003) Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model. J Alzheimers Dis 5:301–308
    • (2003) J Alzheimers Dis , vol.5 , pp. 301-308
    • Perez, M.1    Hernandez, F.2    Lim, F.3    Díaz-Nido, J.4    Avila, J.5
  • 154
    • 0034010742 scopus 로고    scopus 로고
    • Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent
    • COI: 1:CAS:528:DC%2BD3cXotFertA%3D%3D, PID: 10662688
    • Meijer L, Thunnissen AM, White AW, Garnier M, Nikolic M, Tsai LH et al (2000) Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent. Chem Biol 7:51–63
    • (2000) Chem Biol , vol.7 , pp. 51-63
    • Meijer, L.1    Thunnissen, A.M.2    White, A.W.3    Garnier, M.4    Nikolic, M.5    Tsai, L.H.6
  • 155
    • 0033798031 scopus 로고    scopus 로고
    • Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/P25
    • COI: 1:CAS:528:DC%2BD3cXnt1Smtro%3D, PID: 10998059
    • Leost M, Schultz C, Link A, Wu YZ, Biernat J, Mandelkow EM et al (2000) Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/P25. Eur J Biochem 267:5983–5994
    • (2000) Eur J Biochem , vol.267 , pp. 5983-5994
    • Leost, M.1    Schultz, C.2    Link, A.3    Wu, Y.Z.4    Biernat, J.5    Mandelkow, E.M.6
  • 156
    • 0035808457 scopus 로고    scopus 로고
    • Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors?
    • COI: 1:CAS:528:DC%2BD3MXmtFSnsA%3D%3D, PID: 11013232
    • Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL et al (2001) Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors? J Biol Chem 276:251–260
    • (2001) J Biol Chem , vol.276 , pp. 251-260
    • Leclerc, S.1    Garnier, M.2    Hoessel, R.3    Marko, D.4    Bibb, J.A.5    Snyder, G.L.6
  • 157
    • 2442465965 scopus 로고    scopus 로고
    • Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration
    • COI: 1:CAS:528:DC%2BD2cXktVOkt78%3D, PID: 15147906
    • Li L, Sengupta A, Haque N, Grundke-Iqbal I, Iqbal K (2004) Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration. FEBS Lett 566:261–269
    • (2004) FEBS Lett , vol.566 , pp. 261-269
    • Li, L.1    Sengupta, A.2    Haque, N.3    Grundke-Iqbal, I.4    Iqbal, K.5
  • 158
    • 33745370049 scopus 로고    scopus 로고
    • PP2A in the abnormal hyperphosphorylation of tau and its reversal by memantine
    • COI: 1:CAS:528:DC%2BD28Xms1agsr0%3D, PID: 16806196
    • PP2A in the abnormal hyperphosphorylation of tau and its reversal by memantine. FEBS Lett 580:3973–3979
    • (2006) FEBS Lett , vol.580 , pp. 3973-3979
    • Chohan, M.O.1    Khatoon, S.2    Iqbal, I.G.3    Iqbal, K.4
  • 159
    • 78650746798 scopus 로고    scopus 로고
    • Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling
    • COI: 1:CAS:528:DC%2BC3cXhs1SqurfF, PID: 21098287
    • Kickstein E, Krauss S, Thornhill P, Rutschow D, Zeller R, Sharkey J et al (2010) Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci USA 107:21830–21835
    • (2010) Proc Natl Acad Sci USA , vol.107 , pp. 21830-21835
    • Kickstein, E.1    Krauss, S.2    Thornhill, P.3    Rutschow, D.4    Zeller, R.5    Sharkey, J.6
  • 160
  • 162
    • 10144260033 scopus 로고    scopus 로고
    • A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region
    • PID: 8872470
    • Guimerá J, Casas C, Pucharcos C, Solans A, Domènech A, Planas AM et al (1996) A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet 5:1305–1310
    • (1996) Hum Mol Genet , vol.5 , pp. 1305-1310
    • Guimerá, J.1    Casas, C.2    Pucharcos, C.3    Solans, A.4    Domènech, A.5    Planas, A.M.6
  • 163
    • 70350512022 scopus 로고    scopus 로고
    • Function and regulation of DYRK1A: towards understanding Down syndrome
    • COI: 1:CAS:528:DC%2BD1MXhtFOhsrnF, PID: 19685005
    • Park J, Song WJ, Chung KC (2009) Function and regulation of DYRK1A: towards understanding Down syndrome. Cell Mol Life Sci 66:3235–3240
    • (2009) Cell Mol Life Sci , vol.66 , pp. 3235-3240
    • Park, J.1    Song, W.J.2    Chung, K.C.3
  • 164
    • 78651061790 scopus 로고    scopus 로고
    • The role of DYRK1A in neurodegenerative diseases
    • COI: 1:CAS:528:DC%2BC3MXhtFGru7o%3D, PID: 21156028
    • Wegiel J, Gong CX, Hwang YW (2011) The role of DYRK1A in neurodegenerative diseases. FEBS J 278:236–245
    • (2011) FEBS J , vol.278 , pp. 236-245
    • Wegiel, J.1    Gong, C.X.2    Hwang, Y.W.3
  • 165
    • 39749196069 scopus 로고    scopus 로고
    • Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BD1cXjtFCntLc%3D, PID: 18005339
    • Ryoo SR, Cho HJ, Lee HW, Jeong HK, Radnaabazar C, Kim YS et al (2008) Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer’s disease. J Neurochem 104:1333–1344
    • (2008) J Neurochem , vol.104 , pp. 1333-1344
    • Ryoo, S.R.1    Cho, H.J.2    Lee, H.W.3    Jeong, H.K.4    Radnaabazar, C.5    Kim, Y.S.6
  • 166
    • 78651063834 scopus 로고    scopus 로고
    • DYRK1A mediated phosphorylation of presenilin-1: a functional link between down syndrome and Alzheimer’s disease
    • COI: 1:CAS:528:DC%2BC3cXhtlGlsb%2FJ, PID: 20456003
    • Ryu YS, Park SY, Jung MS, Yoon SH, Kwen MY, Lee SY et al (2010) DYRK1A mediated phosphorylation of presenilin-1: a functional link between down syndrome and Alzheimer’s disease. J Neurochem 115:574–584
    • (2010) J Neurochem , vol.115 , pp. 574-584
    • Ryu, Y.S.1    Park, S.Y.2    Jung, M.S.3    Yoon, S.H.4    Kwen, M.Y.5    Lee, S.Y.6
  • 167
    • 33846533244 scopus 로고    scopus 로고
    • The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease
    • COI: 1:CAS:528:DC%2BD2sXotVWksA%3D%3D, PID: 17135279
    • Kimura R, Kamino K, Yamamoto M, Nuripa A, Kida T, Kazui H et al (2007) The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease. Hum Mol Genet 16:15–23
    • (2007) Hum Mol Genet , vol.16 , pp. 15-23
    • Kimura, R.1    Kamino, K.2    Yamamoto, M.3    Nuripa, A.4    Kida, T.5    Kazui, H.6
  • 168
    • 26944433068 scopus 로고    scopus 로고
    • Constitutive DYRK1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models
    • COI: 1:CAS:528:DC%2BD2MXhtFCjs7bN, PID: 16242644
    • Ferrer I, Barrachina M, Puig B, Martínez de Lagrán M, Martí E, Avila J et al (2005) Constitutive DYRK1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 20:392–400
    • (2005) Neurobiol Dis , vol.20 , pp. 392-400
    • Ferrer, I.1    Barrachina, M.2    Puig, B.3    Martínez de Lagrán, M.4    Martí, E.5    Avila, J.6
  • 169
    • 36549040859 scopus 로고    scopus 로고
    • The selectivity of protein kinase inhibitors: a further update
    • COI: 1:CAS:528:DC%2BD2sXhtlGmtbjE, PID: 17850214
    • Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H et al (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408:297–315
    • (2007) Biochem J , vol.408 , pp. 297-315
    • Bain, J.1    Plater, L.2    Elliott, M.3    Shpiro, N.4    Hastie, C.J.5    McLauchlan, H.6
  • 170
    • 79955827792 scopus 로고    scopus 로고
    • β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites
    • COI: 1:CAS:528:DC%2BC3MXmtFKjurY%3D, PID: 21573099
    • Frost D, Meechoovet B, Wang T, Gately S, Giorgetti M, Shcherbakova I et al (2011) β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites. PLoS One 6:e19264
    • (2011) PLoS One , vol.6
    • Frost, D.1    Meechoovet, B.2    Wang, T.3    Gately, S.4    Giorgetti, M.5    Shcherbakova, I.6
  • 171
    • 77950260663 scopus 로고    scopus 로고
    • Two new peltogynoids from Acacia nilotica delile with kinase inhibitory activity
    • COI: 1:CAS:528:DC%2BC3cXltFSkt7Y%3D, PID: 19844867
    • Ahmadu A, Abdulkarim A, Grougnet R, Myrianthopoulos V, Tillequin F, Magiatis P et al (2010) Two new peltogynoids from Acacia nilotica delile with kinase inhibitory activity. Planta Med 76:458–460
    • (2010) Planta Med , vol.76 , pp. 458-460
    • Ahmadu, A.1    Abdulkarim, A.2    Grougnet, R.3    Myrianthopoulos, V.4    Tillequin, F.5    Magiatis, P.6
  • 172
    • 0037392942 scopus 로고    scopus 로고
    • The specificities of protein kinase inhibitors: an update
    • COI: 1:CAS:528:DC%2BD3sXitlCitrg%3D, PID: 12534346
    • Bain J, McLauchlan H, Elliott M, Cohen P (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371:199–204
    • (2003) Biochem J , vol.371 , pp. 199-204
    • Bain, J.1    McLauchlan, H.2    Elliott, M.3    Cohen, P.4
  • 173
    • 79959406830 scopus 로고    scopus 로고
    • Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing
    • COI: 1:CAS:528:DC%2BC3MXmslGls7o%3D, PID: 21615147
    • Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P et al (2011) Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem 54:4172–4186
    • (2011) J Med Chem , vol.54 , pp. 4172-4186
    • Debdab, M.1    Carreaux, F.2    Renault, S.3    Soundararajan, M.4    Fedorov, O.5    Filippakopoulos, P.6
  • 174
    • 84868530112 scopus 로고    scopus 로고
    • Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B
    • COI: 1:CAS:528:DC%2BC38Xhtl2mu7vF, PID: 22998443
    • Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E et al (2012) Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B. J Med Chem 55:9312–9330
    • (2012) J Med Chem , vol.55 , pp. 9312-9330
    • Tahtouh, T.1    Elkins, J.M.2    Filippakopoulos, P.3    Soundararajan, M.4    Burgy, G.5    Durieu, E.6
  • 175
    • 79960196093 scopus 로고    scopus 로고
    • Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives
    • COI: 1:CAS:528:DC%2BC3MXnt12nsb4%3D, PID: 21623630
    • Giraud F, Alves G, Debiton E, Nauton L, Théry V, Durieu E et al (2011) Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives. J Med Chem 54:4474–4489
    • (2011) J Med Chem , vol.54 , pp. 4474-4489
    • Giraud, F.1    Alves, G.2    Debiton, E.3    Nauton, L.4    Théry, V.5    Durieu, E.6
  • 177
    • 84901664872 scopus 로고    scopus 로고
    • Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors
    • COI: 1:CAS:528:DC%2BC2cXnsFSksbo%3D, PID: 24798019
    • Beniddir MA, Le Borgne E, Iorga BI, Loaec N, Lozach O, Meijer L et al (2014) Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors. J Nat Prod 77:1117–1122
    • (2014) J Nat Prod , vol.77 , pp. 1117-1122
    • Beniddir, M.A.1    Le Borgne, E.2    Iorga, B.I.3    Loaec, N.4    Lozach, O.5    Meijer, L.6
  • 178
    • 71749110422 scopus 로고    scopus 로고
    • Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk)
    • COI: 1:CAS:528:DC%2BD1MXhtlGisLfE, PID: 19837585
    • Mott BT, Tanega C, Shen M, Maloney DJ, Shinn P, Leister W et al (2009) Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk). Bioorg Med Chem Lett 19:6700–6705
    • (2009) Bioorg Med Chem Lett , vol.19 , pp. 6700-6705
    • Mott, B.T.1    Tanega, C.2    Shen, M.3    Maloney, D.J.4    Shinn, P.5    Leister, W.6
  • 179
    • 79955567813 scopus 로고    scopus 로고
    • Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk)
    • COI: 1:CAS:528:DC%2BC3MXlsVCls7o%3D, PID: 21450467
    • Rosenthal AS, Tanega C, Shen M, Mott BT, Bougie JM, Nguyen DT et al (2011) Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk). Bioorg Med Chem Lett 21:3152–3158
    • (2011) Bioorg Med Chem Lett , vol.21 , pp. 3152-3158
    • Rosenthal, A.S.1    Tanega, C.2    Shen, M.3    Mott, B.T.4    Bougie, J.M.5    Nguyen, D.T.6
  • 180
    • 79951954356 scopus 로고    scopus 로고
    • Development of a novel selective inhibitor of the Down syndrome-related kinase DYRK1A
    • Ogawa Y, Nonaka Y, Goto T, Ohnishi E, Hiramatsu T, Kii I et al (2010) Development of a novel selective inhibitor of the Down syndrome-related kinase DYRK1A. Nat Commun 86:1–9
    • (2010) Nat Commun , vol.86 , pp. 1-9
    • Ogawa, Y.1    Nonaka, Y.2    Goto, T.3    Ohnishi, E.4    Hiramatsu, T.5    Kii, I.6
  • 181
    • 39749165071 scopus 로고    scopus 로고
    • Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex
    • COI: 1:CAS:528:DC%2BD1cXhtl2msL8%3D, PID: 18232649
    • Echalier A, Bettayeb K, Ferandin Y, Lozach O, Clément M, Valette A et al (2008) Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex. J Med Chem 51:737–751
    • (2008) J Med Chem , vol.51 , pp. 737-751
    • Echalier, A.1    Bettayeb, K.2    Ferandin, Y.3    Lozach, O.4    Clément, M.5    Valette, A.6
  • 182
    • 84857236110 scopus 로고    scopus 로고
    • Synthesis of chromeno [3,4-b]indoles as Lamellarin D analogues: a novel DYRK1A inhibitor class
    • COI: 1:CAS:528:DC%2BC38XisFOrsLs%3D, PID: 22305342
    • Neagoie C, Vedrenne E, Buron F, Mérour JY, Rosca S, Bourg S et al (2012) Synthesis of chromeno [3,4-b]indoles as Lamellarin D analogues: a novel DYRK1A inhibitor class. Eur J Med Chem 49:379–396
    • (2012) Eur J Med Chem , vol.49 , pp. 379-396
    • Neagoie, C.1    Vedrenne, E.2    Buron, F.3    Mérour, J.Y.4    Rosca, S.5    Bourg, S.6
  • 183
    • 84907970245 scopus 로고    scopus 로고
    • Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors
    • COI: 1:CAS:528:DC%2BC2cXhsFOltLfE, PID: 25248682
    • Bruel A, Bénéteau R, Chabanne M, Lozach O, Le Guevel R, Ravache M et al (2014) Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors. Bioorg Med Chem Lett 24:5037–5040
    • (2014) Bioorg Med Chem Lett , vol.24 , pp. 5037-5040
    • Bruel, A.1    Bénéteau, R.2    Chabanne, M.3    Lozach, O.4    Le Guevel, R.5    Ravache, M.6
  • 184
    • 0027209389 scopus 로고
    • Strategies of antioxidant defense
    • COI: 1:CAS:528:DyaK3sXltlKms7w%3D, PID: 7688300
    • Sies H (1993) Strategies of antioxidant defense. Eur J Biochem 215:213–219
    • (1993) Eur J Biochem , vol.215 , pp. 213-219
    • Sies, H.1
  • 185
    • 0032733691 scopus 로고    scopus 로고
    • The role of oxidative stress in Alzheimer disease
    • COI: 1:STN:280:DC%2BD3c%2FlvVyksw%3D%3D, PID: 10593298
    • Markesbery WR (1999) The role of oxidative stress in Alzheimer disease. Arch Neurol 56:1449–1452
    • (1999) Arch Neurol , vol.56 , pp. 1449-1452
    • Markesbery, W.R.1
  • 187
    • 0031558654 scopus 로고    scopus 로고
    • Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer’s disease brain
    • COI: 1:CAS:528:DyaK2sXntlCitb8%3D, PID: 9452208
    • Su JH, Deng G, Cotman CW (1997) Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer’s disease brain. Brain Res 774:193–199
    • (1997) Brain Res , vol.774 , pp. 193-199
    • Su, J.H.1    Deng, G.2    Cotman, C.W.3
  • 188
    • 0035405886 scopus 로고    scopus 로고
    • Metalloproteinases in biology and pathology of the nervous system
    • Young VW, Power C, Forsyth P, Edwards DR (2001) Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2:502–511
    • (2001) Nat Rev Neurosci , vol.2 , pp. 502-511
    • Young, V.W.1    Power, C.2    Forsyth, P.3    Edwards, D.R.4
  • 190
    • 0346688728 scopus 로고    scopus 로고
    • Cache county study group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the cache county study
    • PID: 14732624
    • Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT et al (2004) Cache county study group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the cache county study. Arch Neurol 61:82–88
    • (2004) Arch Neurol , vol.61 , pp. 82-88
    • Zandi, P.P.1    Anthony, J.C.2    Khachaturian, A.S.3    Stone, S.V.4    Gustafson, D.5    Tschanz, J.T.6
  • 191
    • 0034122940 scopus 로고    scopus 로고
    • The Ginkgo biloba extract (Egb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase
    • COI: 1:CAS:528:DC%2BD3cXjsVKku7o%3D, PID: 10820186
    • Bastianetto S, Zheng WH, Quirion R (2000) The Ginkgo biloba extract (Egb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase. J Neurochem 74:2268–2277
    • (2000) J Neurochem , vol.74 , pp. 2268-2277
    • Bastianetto, S.1    Zheng, W.H.2    Quirion, R.3
  • 192
    • 0037098866 scopus 로고    scopus 로고
    • Antioxidant neuroprotection in Alzheimer’s disease as preventive and therapeutic approach
    • COI: 1:CAS:528:DC%2BD38XmsVekt7s%3D, PID: 12106814
    • Behl C, Moosmann B (2002) Antioxidant neuroprotection in Alzheimer’s disease as preventive and therapeutic approach. Free Radic Biol Med 33:182–191
    • (2002) Free Radic Biol Med , vol.33 , pp. 182-191
    • Behl, C.1    Moosmann, B.2
  • 193
    • 79958061878 scopus 로고    scopus 로고
    • Antioxidant effects of green tea
    • COI: 1:CAS:528:DC%2BC3MXmvFCntbg%3D, PID: 21538850
    • Forester SC, Lambert JD (2011) Antioxidant effects of green tea. Mol Nutr Food Res 55:844–854
    • (2011) Mol Nutr Food Res , vol.55 , pp. 844-854
    • Forester, S.C.1    Lambert, J.D.2
  • 194
    • 75349090576 scopus 로고    scopus 로고
    • Ginkgo biloba extract in Alzheimer’s disease: from action mechanisms to medical practice
    • COI: 1:CAS:528:DC%2BC3cXhtVyhs7c%3D, PID: 20162004
    • Shi C, Liu J, Wu F, Yew DT (2010) Ginkgo biloba extract in Alzheimer’s disease: from action mechanisms to medical practice. Int J Mol Sci 11:107–123
    • (2010) Int J Mol Sci , vol.11 , pp. 107-123
    • Shi, C.1    Liu, J.2    Wu, F.3    Yew, D.T.4
  • 195
    • 69149104713 scopus 로고    scopus 로고
    • Anti-Alzheimer and antioxidant activities of Coptidis rhizoma alkaloids
    • COI: 1:CAS:528:DC%2BD1MXhtFCjsLbO, PID: 19652386
    • Jung HA, Min BS, Yokozawa T, Lee JH, Kim YS, Choi JS (2009) Anti-Alzheimer and antioxidant activities of Coptidis rhizoma alkaloids. Biol Pharm Bull 32:1433–1438
    • (2009) Biol Pharm Bull , vol.32 , pp. 1433-1438
    • Jung, H.A.1    Min, B.S.2    Yokozawa, T.3    Lee, J.H.4    Kim, Y.S.5    Choi, J.S.6
  • 197
    • 84983523117 scopus 로고    scopus 로고
    • Neuroinflammation in Alzheimer’s disease: current evidence and future directions
    • Calsolaro V, Edison P (2016) Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement S1552–5260:30185–30186
    • (2016) Alzheimers Dement , vol.S1552–5260 , pp. 30185-30186
    • Calsolaro, V.1    Edison, P.2
  • 199
    • 31044445398 scopus 로고    scopus 로고
    • Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPAR gamma
    • COI: 1:CAS:528:DC%2BD28XpsVSluw%3D%3D, PID: 16407166
    • Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P et al (2006) Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPAR gamma. Proc Natl Acad Sci USA 103:443–448
    • (2006) Proc Natl Acad Sci USA , vol.103 , pp. 443-448
    • Sastre, M.1    Dewachter, I.2    Rossner, S.3    Bogdanovic, N.4    Rosen, E.5    Borghgraef, P.6
  • 201
    • 47549107705 scopus 로고    scopus 로고
    • Cognitive function over time in the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib
    • ADAPT Research Group, Martin BK, Szekely C, Brandt J, Piantadosi S, Breitner JC, Craft S et al (2008) Cognitive function over time in the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 65:896–905
    • (2008) Arch Neurol , vol.65 , pp. 896-905
    • ADAPT Research Group1    Martin, B.K.2    Szekely, C.3    Brandt, J.4    Piantadosi, S.5    Breitner, J.C.6    Craft, S.7
  • 203
    • 84928434453 scopus 로고    scopus 로고
    • Cholesterol, statins, and dementia: what the cardiologist should know
    • PID: 25869997
    • Wanamaker BL, Swiger KJ, Blumenthal RS, Martin SS (2015) Cholesterol, statins, and dementia: what the cardiologist should know. Clin Cardiol 38:243–250
    • (2015) Clin Cardiol , vol.38 , pp. 243-250
    • Wanamaker, B.L.1    Swiger, K.J.2    Blumenthal, R.S.3    Martin, S.S.4
  • 205
    • 77949908687 scopus 로고    scopus 로고
    • Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe
    • COI: 1:CAS:528:DC%2BC3cXjs1Ggsb4%3D, PID: 20200346
    • Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW et al (2010) Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 74:956–964
    • (2010) Neurology , vol.74 , pp. 956-964
    • Feldman, H.H.1    Doody, R.S.2    Kivipelto, M.3    Sparks, D.L.4    Waters, D.D.5    Jones, R.W.6


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.