Targeting amyloid precursor protein secretases: Alzheimer's disease and beyond

Drug News and Perspectives

Volumn 23, Issue 9, 2010, Pages 573-584

  Ganjei, J Kelly ^a  

^a RemeGenix Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEGACESTAT; BETA SECRETASE INHIBITOR; CTS 21166; HOMOTAURINE; NONSTEROID ANTIINFLAMMATORY AGENT; SECRETASE; SEMAGACESTAT; TARENFLURBIL; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; COGNITION; DISEASE COURSE; DISEASE SEVERITY; DRUG BRAIN LEVEL; DRUG EFFICACY; DRUG MECHANISM; HUMAN; INTERVIEW; NONHUMAN; PROTEIN DOMAIN; RATING SCALE; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CLINICAL TRIAL (TOPIC); DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG SCREENING; METABOLISM; METHODOLOGY; PATHOPHYSIOLOGY;

ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS;

EID: 79952278055     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2010.23.9.1507297     Document Type: Review

References (111)

1. Hardy, J. A hundred years of Alzheimer's disease research. Neuron 2006, 52(1): 3-13. (Pubitemid 44472602)
2. Bertram, L., Tanzi, R.E. Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008, 9(10): 768-78.
3. Breteler, M.M., Claus, J.J., van Duijn, C.M., Launer, L.J., Hofman, A. Epidemiology of Alzheimer's disease. Epidemiol Rev 1992, 14: 59-82. (Pubitemid 23024554)
4. Brookmeyer, R., Gray, S., Kawas, C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health 1998, 88(9): 1337-42. (Pubitemid 28402270)
5. Are there other treatments for cognitive decline? Fisher Center for Alzheimer's Research Foundation. http://www.alzinfo.org/alzheimers-treatment- cognitive.asp. Accessed November 9, 2010.
6. Nordberg, A. Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis Assoc Disord 2006, 20(2 Suppl 1): S12-8.
7. Alley, G.M., Bailey, J.A., Chen, D. et al. Memantine lowers amyloid-beta peptide levels in neuronal cultures and in APP/PS1 transgenic mice. J Neurosci Res 2010, 88(1): 143-54.
8. Martinez-Coria, H., Green, K.N., Billings, L.M. et al. Memantine improves cognition and reduces Alzheimer's-like neuropathology in transgenic mice. Am J Pathol 2010, 176(2): 870-80.
9. Arif, M., Chikuma, T., Ahmed, M.M., Nakazato, M., Smith, M.A., Kato, T. Effects of memantine on soluble Alphabeta(25-35)-induced changes in peptidergic and glial cells in Alzheimer's disease model rat brain regions. Neuroscience 2009, 164(3): 1199-209.
10. Guardia-Laguarta, C., Coma, M., Pera, M. et al. Mild cholesterol depletion reduces amyloid-beta production by impairing APP trafficking to the cell surface. J Neurochem 2009, 110(1): 220-30.
11. Chan, A., Tchantchou, F., Rogers, E.J., Shea, T.B. Dietary deficiency increases presenilin expression, gamma-secretase activity, and Abeta levels: potentiation by ApoE genotype and alleviation by S-adenosyl methionine. J Neurochem 2009, 110(3): 831-6.
12. Small, S.A., Duff, K. Linking Abeta and tau in late-onset Alzheimer's disease: a dual pathway hypothesis. Neuron 2008, 60(4): 534-42.
13. Wray, S., Noble, W. Linking amyloid and tau pathology in Alzheimer's disease: the role of membrane cholesterol in Abeta-mediated tau toxicity. J Neurosci 2009, 29(31): 9665-7.
14. Bales, K.R., Dodart, J.C., DeMattos, R.B., Holtzman, D.M., Paul, S.M. Apolipoprotein E, amyloid, and Alzheimer disease. Mol Interv 2002, 2(6): 363-75, 39.
15. DeMattos, R.B., Cirrito, J.R., Parsadanian, M. et al. ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo. Neuron 2004, 41(2): 193-202. (Pubitemid 38125181)
16. Dodart, J.C., Marr, R.A., Koistinaho, M., Gregersen, B.M., Malkani, S., Verma, I.M., Paul, S.M. Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 2005, 102(4): 1211-6. (Pubitemid 40170751)
17. Bi, X., Yong, A.P., Zhou, J., Ribak, C.E., Lynch, G. Rapid induction of intraneuronal neurofibrillary tangles in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A 2001, 98(15): 8832-7. (Pubitemid 32678113)
18. Brecht, W.J., Harris, F.M., Chang, S. et al. Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J Neurosci 2004, 24(10): 2527-34. (Pubitemid 38327965)
19. Genis, L., Chen, Y., Shohami, E., Michaelson, D.M. Tau hyperphosphorylation in apolipoprotein E-deficient and control mice after closed head injury. J Neurosci Res 2000, 60(4): 559-64. (Pubitemid 30252919)
20. Harris, F.M., Brecht, W.J., Xu, Q., Mahley, R.W., Huang, Y. Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase: modulation by zinc. J Biol Chem 2004, 279(43): 44795-801. (Pubitemid 39430890)
21. Harris, F.M., Brecht, W.J., Xu, Q. et al. Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc Natl Acad Sci U S A 2003, 100(19): 10966-71. (Pubitemid 37140136)
22. Ohkubo, N., Lee, Y.D., Morishima, A. et al. Apolipoprotein E and Reelin ligands modulate tau phosphorylation through an apolipoprotein E receptor/disabled-1/glycogen synthase kinase-3beta cascade. FASEB J 2003, 17(2): 295-7.
23. Jankowsky, J.L., Slunt, H.H., Gonzales, V., Jenkins, N.A., Copeland, N.G., Borchelt, D.R. APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiol Aging 2004, 25(7): 885-92. (Pubitemid 38813168)
24. Jankowsky, J.L., Fadale, D.J., Anderson, J. et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 2004, 13(2): 159-70. (Pubitemid 38111354)
25. Aguzzi, A., O'Connor, T. Protein aggregation diseases: pathogenicity and therapeutic perspectives. Nat Rev Drug Discov 2010, 9(3): 237-48.
26. Kalaria, R.N. Comparison between Alzheimer's disease and vascular dementia: implications for treatment. Neurol Res 2003, 25(6): 661-4. (Pubitemid 37087611)
27. Price, J.M., Hellermann, A., Hellermann, G., Sutton, E.T. Aging enhances vascular dysfunction induced by the Alzheimer's peptide beta-amyloid. Neurol Res 2004, 26(3): 305-11. (Pubitemid 38620051)
28. van Es, M.A., van den Berg, L.H. Alzheimer's disease beyond APOE. Nat Genet 2009, 41(10): 1047-8.
29. Bush, A.I., Tanzi, R.E. Therapeutics for Alzheimer's disease based on the metal hypothesis. Neurotherapeutics 2008, 5(3): 421-32. (Pubitemid 351952485)
30. Willem, M., Garratt, A.N., Novak, B. et al. Control of peripheral nerve myelination by the beta-secretase BACE1. Science 2006, 314(5799): 664-6. (Pubitemid 44646394)
31. Hu, X., Hicks, C.W., He, W., Wong, P., Macklin, W.B., Trapp, B.D., Yan, R. Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci 2006, 9(12): 1520-5. (Pubitemid 44862660)
32. Sankaranarayanan, S., Price, E.A., Wu, G. et al. In vivo beta-secretase 1 inhibition leads to brain Abeta lowering and increased alpha-secretase processing of amyloid precursor protein without effect on neuregulin-1. J Pharmacol Exp Ther 2008, 324(3): 957-69.
33. Harrison, S.M., Harper, A.J., Hawkins, J. et al. BACE1 (beta-secretase) transgenic and knockout mice: identification of neurochemical deficits and behavioral changes. Mol Cell Neurosci 2003, 24(3): 646-55. (Pubitemid 37506009)
34. Lesne, S., Koh, M.T., Kotilinek, L. et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006, 440(7082): 352-7.
35. Deacon, R.M., Cholerton, L.L., Talbot, K. et al. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav Brain Res 2008, 189(1): 126-38.
36. Kawarabayashi, T., Younkin, L.H., Saido, T.C., Shoji, M., Ashe, K.H., Younkin, S.G. Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 2001, 21(2): 372-81. (Pubitemid 32107428)
37. Reed, M.N., Liu, P., Kotilinek, L.A., Ashe, K.H. Effect size of reference memory deficits in the Morris water maze in Tg2576 mice. Behav Brain Res 2010, 212(1): 115-20.
38. Westerman, M.A., Cooper-Blacketer, D., Mariash, A. et al. The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 2002, 22(5): 1858-67. (Pubitemid 35386304)
39. Shankar, G.M., Li, S., Mehta, T.H. et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 2008, 14(8): 837-42.
40. Tomiyama, T., Matsuyama, S., Iso, H. et al. A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo. J Neurosci 2010, 30(14): 4845-56.
41. Li, S., Hong, S., Shepardson, N.E., Walsh, D.M., Shankar, G.M., Selkoe, D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 2009, 62(6): 788-801.
42. Puzzo, D., Staniszewski, A., Deng, S.X. et al. Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid-beta load in an Alzheimer's disease mouse model. J Neurosci 2009, 29(25): 8075-86.
43. Citron, M. Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov 2010, 9(5): 387-98.
44. Patton, R.L., Kalback, W.M., Esh, C.L. et al. Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis. Am J Pathol 2006, 169(3): 1048-63. (Pubitemid 44411966)
45. Citron, M. Strategies for disease modification in Alzheimer's disease. Nat Rev Neurosci 2004, 5(9): 677-85. (Pubitemid 39150139)
46. Fagan, A.M., Watson, M., Parsadanian, M., Bales, K.R., Paul, S.M., Holtzman, D.M. Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Neurobiol Dis 2002, 9(3): 305-18. (Pubitemid 34442079)
47. Duff, K. Transgenic mouse models of Alzheimer's disease: phenotype and mechanisms of pathogenesis. Biochem Soc Symp 2001(67): 195-202. (Pubitemid 33602686)
48. Kim, S.H., Wang, R., Gordon, D.J. et al. Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia. Nat Neurosci 1999, 2(11): 984-8. (Pubitemid 30599561)
49. Vidal, R., Frangione, B., Rostagno, A., Mead, S., Revesz, T., Plant, G., Ghiso, J. A stop-codon mutation in the BRI gene associated with familial British dementia. Nature 1999, 399(6738): 776-81. (Pubitemid 29293172)
50. Ghiso, J., Vidal, R., Rostagno, A. et al. Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13. Ann N Y Acad Sci 2000, 920: 84-92. (Pubitemid 32056555)
51. Vidal, R., Revesz, T., Rostagno, A. et al. A decamer duplication in the 3′ region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. Proc Natl Acad Sci U S A 2000, 97(9): 4920-5. (Pubitemid 30238658)
52. Ghiso, J.A., Holton, J., Miravalle, L. et al. Systemic amyloid deposits in familial British dementia. J Biol Chem 2001, 276(47): 43909-14.
53. Akiyama, H., Kondo, H., Arai, T. et al. Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain. Acta Neuropathol (Berl) 2004, 107(1): 53-8. (Pubitemid 38088275)
54. Lesne, S., Kotilinek, L., Ashe, K.H. Plaque-bearing mice with reduced levels of oligomeric amyloid-beta assemblies have intact memory function. Neuroscience 2008, 151(3): 745-9.
55. Ashe, K.H. Molecular basis of memory loss in the Tg2576 mouse model of Alzheimer's disease. J Alzheimers Dis 2006, 9(3 Suppl): 123-6. (Pubitemid 44253305)
56. Benzing, W.C., Wujek, J.R., Ward, E.K., Shaffer, D., Ashe, K.H., Younkin, S.G., Brunden, K.R. Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol Aging 1999, 20(6): 581-9. (Pubitemid 30064403)
57. Cole, S.L., Vassar, R. The Alzheimer's disease beta-secretase enzyme, BACE1. Mol Neurodegener 2007, 2: 22.
58. Strobel, G. Keystone Drug News: CoMentis BACE Inhibitor Debuts. http://www.alzforum.org/new/detail.asp?id=1790. Accessed November 9, 2010.
59. Study of the pharmacokinetics and pharmacodynamics of Posiphen(R) in subjects with amnestic mild cognitive impairment (NCT01072812). ClinicalTrials.gov Web site, Accessed November 9, 2010.
60. Lahiri, D.K., Chen, D., Maloney, B. et al. The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice. J Pharmacol Exp Ther 2007, 320(1): 386-96. (Pubitemid 46025753)
61. Xu, J., Litterst, C., Georgakopoulos, A., Zaganas, I., Robakis, N.K. Peptide EphB2/CTF2 generated by the gamma-secretase processing of EphB2 receptor promotes tyrosine phosphorylation and cell surface localization of N-methyl-D-aspartate receptors. J Biol Chem 2009, 284(40): 27220-8.
62. Lilly halts development of semagacestat for Alzheimer's disease based on preliminary results of phase III clinical trials [news release]. Eli Lilly and Company, August 17, 2010. http://newsroom.lilly.com/releasedetail.cfm?ReleaseID= 499794. Accessed November 9, 2010.
63. Pfizer Pipeline as of September 27, 2010. http://media.pfizer.com/files/ research/pipeline/2010-0927/pipeline-2010-0927.pdf. Accessed November 9, 2010.
64. Tamboli, I.Y., Prager, K., Thal, D.R. et al. Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis. J Neurosci 2008, 28(46): 12097-106.
65. Fuentealba, R.A., Barria, M.I., Lee, J. et al. ApoER2 expression increases Abeta production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of gamma-secretase activity. Mol Neurodegener 2007, 2: 14.
66. Liu, Q., Zerbinatti, C.V., Zhang, J. et al. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron 2007, 56(1): 66-78. (Pubitemid 47484175)
67. Rasul, S., Balasubramanian, R., Filipovic, A., Slade, M.J., Yague, E., Coombes, R.C. Inhibition of gamma-secretase induces G2/M arrest and triggers apoptosis in breast cancer cells. Br J Cancer 2009, 100(12): 1879-88.
68. Hemming, M.L., Elias, J.E., Gygi, S.P., Selkoe, D.J. Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biol 2008, 6(10): e257.
69. Marks, N., Berg, M.J. BACE and gamma-secretase characterization and their sorting as therapeutic targets to reduce amyloidogenesis. Neurochem Res 2010, 35(2): 181-210.
70. Brody, D.L., Holtzman, D.M. Active and passive immunotherapy for neurodegenerative disorders. Annu Rev Neurosci 2008, 31: 175-93.
71. Taguchi, H., Planque, S., Nishiyama, Y. et al. Autoantibody-catalyzed hydrolysis of amyloid beta peptide. J Biol Chem 2008, 283(8): 4714-22.
72. Nitsch, R.M., Hock, C. Targeting beta-amyloid pathology in Alzheimer's disease with Abeta immunotherapy. Neurotherapeutics 2008, 5(3): 415-20. (Pubitemid 351952496)
73. Nicoll, J.A., Wilkinson, D., Holmes, C., Steart, P., Markham, H., Weller, R.O. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 2003, 9(4): 448-52. (Pubitemid 36460079)
74. Orgogozo, J.M., Gilman, S., Dartigues, J.F. et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003, 61(1): 46-54. (Pubitemid 36818745)
75. Holmes, C., Boche, D., Wilkinson, D. et al. Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 2008, 372(9634): 216-23. (Pubitemid 351978111)
76. Oddo, S., Vasilevko, V., Caccamo, A., Kitazawa, M., Cribbs, D.H., LaFerla, F.M. Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem 2006, 281(51): 39413-23. (Pubitemid 46041901)
77. Oddo, S., Caccamo, A., Smith, I.F., Green, K.N., LaFerla, F.M. A dynamic relationship between intracellular and extracellular pools of Abeta. Am J Pathol 2006, 168(1): 184-94. (Pubitemid 43062572)
78. Schmidt, A.M., Sahagan, B., Nelson, R.B., Selmer, J., Rothlein, R., Bell, J.M. The role of RAGE in amyloid-beta peptide-mediated pathology in Alzheimer's disease. Curr Opin Investig Drugs 2009, 10(7): 672-80.
79. Nikolaev, A., McLaughlin, T., O'Leary, D.D., Tessier-Lavigne, M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 2009, 457(7232): 981-9.
80. Muller, T., Concannon, C.G., Ward, M.W. et al. Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD). Mol Biol Cell 2007, 18(1): 201-10. (Pubitemid 46066721)
81. Muller, T., Meyer, H.E., Egensperger, R., Marcus, K. The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog Neurobiol 2008, 85(4): 393-406.
82. Ozaki, T., Li, Y., Kikuchi, H., Tomita, T., Iwatsubo, T., Nakagawara, A. The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis. Biochem Biophys Res Commun 2006, 351(1): 57-63. (Pubitemid 44635406)
83. Trinchese, F., Fa, M., Liu, S. et al. Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease. J Clin Invest 2008, 118(8): 2796-807.
84. Veeranna, Kaji, T., Boland, B. et al. Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease. Am J Pathol 2004, 165(3): 795-805. (Pubitemid 39129287)
85. Passer, B., Pellegrini, L., Russo, C. et al. Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor. J Alzheimers Dis 2000, 2(3-4): 289-301. (Pubitemid 32095613)
86. Eckert, A., Hauptmann, S., Scherping, I. et al. Oligomeric and fibrillar species of beta-amyloid (A beta 42) both impair mitochondrial function in P301L tau transgenic mice. J Mol Med 2008, 86(11): 1255-67.
87. Youssef, I., Florent-Bechard, S., Malaplate-Armand, C. et al. N-truncated amyloid-beta oligomers induce learning impairment and neuronal apoptosis. Neurobiol Aging 2008, 29(9): 1319-33. (Pubitemid 351981997)
88. Reed, M.N., Hofmeister, J.J., Jungbauer, L. et al. Cognitive effects of cell-derived and synthetically derived Abeta oligomers. Neurobiol Aging 2009, Advance publication.
89. Tampellini, D., Rahman, N., Gallo, E.F. et al. Synaptic activity reduces intraneuronal Abeta, promotes APP transport to synapses, and protects against Abeta-related synaptic alterations. J Neurosci 2009, 29(31): 9704-13.
90. Elan and Transition Therapeutics announce modifications to ELND005 phase II clinical trials in Alzheimer's disease [news release]. Elan Corporation, December 15, 2009. http://newsroom.elan.com/phoenix.zhtml?c=88326&p=irol- newsArticle&ID=1365793&highlight=. Accessed November 9, 2010.
91. Sastre, M., Dewachter, I., Rossner, S. et al. Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma. Proc Natl Acad Sci U S A 2006, 103(2): 443-8. (Pubitemid 43122420)
92. Sastre, M., Dewachter, I., Landreth, G.E., Willson, T.M., Klockgether, T., van Leuven, F., Heneka, M.T. Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase. J Neurosci 2003, 23(30): 9796-804. (Pubitemid 37371592)
93. Weggen, S., Eriksen, J.L., Das, P. et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 2001, 414(6860): 212-6. (Pubitemid 33051236)
94. Eriksen, J.L., Sagi, S.A., Smith, T.E. et al. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest 2003, 112(3): 440-9. (Pubitemid 38063773)
95. Imbimbo, B.P. Why did tarenflurbil fail in Alzheimer's disease? J Alzheimers Dis 2009, 17(4): 757-60.
96. Klein, J. Phenserine. Expert Opin Investig Drugs 2007, 16(7): 1087-97.
97. Kadir, A., Andreasen, N., Almkvist, O. et al. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann Neurol 2008, 63(5): 621-31.
98. Barbato, C., Canu, N., Zambrano, N. et al. Interaction of Tau with Fe65 links tau to APP. Neurobiol Dis 2005, 18(2): 399-408. (Pubitemid 40431124)
99. LaFerla, F.M., Oddo, S. Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol Med 2005, 11(4): 170-6.
100. Roberson, E.D., Scearce-Levie, K., Palop, J.J. et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 2007, 316(5825): 750-4. (Pubitemid 46717684)
101. Hanger, D.P., Seereeram, A., Noble, W. Mediators of tau phosphorylation in the pathogenesis of Alzheimer's disease. Expert Rev Neurother 2009, 9(11): 1647-66.
102. Hanger, D.P., Anderton, B.H., Noble, W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 2009, 15(3): 112-9.
103. Giliberto, L., Zhou, D., Weldon, R., Tamagno, E., De Luca, P., Tabaton, M., D'Adamio, L. Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role. Mol Neurodegener 2008, 3: 12.
104. Di Rosa, G., Odrijin, T., Nixon, R.A., Arancio, O. Calpain inhibitors: a treatment for Alzheimer's disease. J Mol Neurosci 2002, 19(1-2): 135-41. (Pubitemid 35013347)
105. Battaglia, F., Trinchese, F., Liu, S., Walter, S., Nixon, R.A., Arancio, O. Calpain inhibitors, a treatment for Alzheimer's disease: position paper. J Mol Neurosci 2003, 20(3): 357-62. (Pubitemid 38146994)
106. Ghersi, E., Vito, P., Lopez, P., Abdallah, M., D'Adamio, L. The intracellular localization of amyloid beta protein precursor (AbetaPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AbetaPP and alternative splicing. J Alzheimers Dis 2004, 6(1): 67-78. (Pubitemid 38418559)
107. Fotinopoulou, A., Tsachaki, M., Vlavaki, M. et al. BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production. J Biol Chem 2005, 280(35): 30768-72. (Pubitemid 41291806)
108. Matsuda, S., Giliberto, L., Matsuda, Y. et al. The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production. J Biol Chem 2005, 280(32): 28912-6. (Pubitemid 41161336)
109. Matsuda, S., Giliberto, L., Matsuda, Y., McGowan, E.M., D'Adamio, L. BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate. J Neurosci 2008, 28(35): 8668-76.
110. Matsuda, S., Matsuda, Y., Snapp, E.L., D'Adamio, L. Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles. Neurobiol Aging 2009, Advance publication.
111. Lourenco, F.C., Galvan, V., Fombonne, J. et al. Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production. Cell Death Differ 2009, 16(5): 655-63.