Slow excitotoxicity in alzheimer's disease

Journal of Alzheimer's Disease

Volumn 35, Issue 4, 2013, Pages 643-668

  Ong, Wei Yi ^a,b   Tanaka, Kazuhiro ^a,b   Dawe, Gavin S ^a,b,c   Ittner, Lars M ^d   Farooqui, Akhlaq A ^e  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c Singapore Institute for Neurotechnology (SINAPSE) 5F   (Singapore)

^d UNIVERSITY OF SYDNEY   (Australia)

^e OHIO STATE UNIVERSITY   (United States)

Author keywords

Alzheimer's disease; amyloid peptide; cholesterd oxidation products; excitotoxicity; insulin resistance; iron; memantine; phospholipase A 2; tau

Indexed keywords

ABC TRANSPORTER; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; APOCYNIN; APOLIPOPROTEIN E; CD2 ASSOCIATED PROTEIN; CERAMIDE; CLATHRIN ASSEMBLY PROTEIN; CLIOQUINOL; CLUSTERIN; COMPLEMENT COMPONENT C3B RECEPTOR; CURCUMIN; DONEPEZIL; EPHRIN; EPHRIN RECEPTOR A1; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; INSULIN RECEPTOR SUBSTRATE 1; IRON; KYNURENINE; MEMANTINE; METFORMIN; MEVINOLIN; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUROSTEROID; PRESENILIN; SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; SIMVASTATIN; SOMATOMEDIN C; TAU PROTEIN;

ALZHEIMER DISEASE; ASTROCYTE; CALCIUM CELL LEVEL; CALCIUM HOMEOSTASIS; ELECTRON SPIN RESONANCE; ENDOPLASMIC RETICULUM STRESS; ENERGY YIELD; EXCITOTOXICITY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENETIC RISK; HUMAN; HYPERCHOLESTEROLEMIA; INSULIN RESISTANCE; INTRACELLULAR SIGNALING; IRON TRANSPORT; MASS FRAGMENTOGRAPHY; MEMBRANE FLUIDITY; MEMORY; METABOLIC SYNDROME X; MICROGLIA; MITOCHONDRION; NERVE CELL; NERVE CELL MEMBRANE STEADY POTENTIAL; NERVE CELL PLASTICITY; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NUCLEIC ACID METABOLISM; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PATHOGENESIS; PHOSPHOLIPID METABOLISM; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SENILE PLAQUE; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84878842182     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-121990     Document Type: Review

References (282)

1. Farooqui AA (2010) Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases, Springer, New York.
2. Farooqui AA(2010) Neurochemical aspects of neuroinflammation in brain. In Molecular Aspects of Neurodegeneration and Neuroprotection, Farooqui AA, Farooqui T, eds. Bentham Science Publishers Ltd.
3. Arlt S, Beisiegel U, Kontush A (2002) Lipid peroxidation in neurodegeneration: New insights into Alzheimer's disease. Curr Opin Lipidol 13, 289-294.
4. Butterfield DA(2002) Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: Implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radical Res 36, 1307-1313.
5. Kontush A (2001) Amyloid-beta: An antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer's disease. Free Radic Biol Med 31, 1120-1131.
6. de la Torre JC (2010) Vascular risk factor detection and control may prevent Alzheimer's disease. Ageing Res Rev 9, 218-225.
7. Bertram L, Tanzi RE (2009) Genome-wide association studies in Alzheimer's disease. Hum Mol Genet 18, R137-R145.
8. Guerreiro RJ, Hardy J (2011) Alzheimer's disease genetics: Lessons to improve disease modelling. Biochem Soc Trans 39, 910-916.
9. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623-634.
10. Olney JW,Wozniak DF, Farber NB (1997) Excitotoxic neurodegeneration in Alzheimer disease. New hypothesis and new therapeutic strategies. Arch Neurol 54, 1234-1240.
11. Farooqui AA, Horrocks LA (1991) Excitatory amino acid receptors, neural membrane phospholipid metabolism and neurological disorders. Brain Res Rev 16, 171-191.
12. Farooqui AA, Horrocks LA (1994) Excitotoxicity and neurological disorders: Involvement of membrane phospholipids. Int Rev Neurobiol 36, 267-323.
13. Phillis JW, Horrocks LA, Farooqui AA (2006) Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: Their role and involvement in neurological disorders. Brain Res Rev 52, 201-243.
14. Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ (1993) Vulnerability of oligodendroglia to glutamate: Pharmacology, mechanisms, and prevention. J Neurosci 13, 1441-1453.
15. Matute C, Domercq M, Sánchez-Gómez MV (2006) Glutamate-mediated glial injury: Mechanisms and clinical importance. Glia 53, 212-224.
16. Auger C, Attwell D (2000) Fast removal of synaptic glutamate by postsynaptic transporters. Neuron 28, 547-558.
17. Farooqui AA, Ong WY, Horrocks LA(2008) Neurochemical Aspects of Excitotoxicity, Springer, New York.
18. Beal MF(1992) Mechanisms of excitotoxicity in neurologic diseases. FASEB J 6, 3338-3344.
19. Novelli A, Reilly JA, Lysko PG, Henneberry RC(1988) Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res 451, 205-212.
20. Zeevalk GD, Nicklas WJ (1990) Chemically induced hypoglycemia and anoxia: Relationship to glutamate receptor-mediated toxicity in retina. J Pharmacol Exp Ther 253, 1285-1292.
21. Beal MF, Swartz KJ, Hyman BT, Storey E, Finn SF, Koroshetz W(1991) Aminooxyacetic acid results in excitotoxin lesions by a novel indirect mechanism. J Neurochem 57, 1068-1073.
22. Storey E, Hyman BT, Jenkins B, Brouillet E, Miller JM, Rosen BR, Beal MF (1992) 1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. J Neurochem 58, 1975-1978.
23. Farooqui AA, Horrocks LA (2006) Phospholipase A2-generated lipid mediators in the brain: The good, the bad, and the ugly. Neuroscientist 12, 245-260.
24. Farooqui AA, Ong WY, Farooqui T (2010) Lipid Mediators in the nucleus: Their potential contribution to Alzheimer's disease. Biochim Biophys Acta 1801, 906-1016.
25. Casado M, Ascher P (1998) Opposite modulation ofNMDA receptors by lysophospholipids and arachidonic acid: Common features with mechanosensitivity. J Physiol 513, 317-330.
26. Iwamoto T, Yamada Y, Hori K, Watanabe Y, Sobue K, Inui M (2004) Differential modulation of NR1-NR2A and NR1-NR2B subtypes of NMDA receptor by PDZ domaincontaining proteins. J Neurochem 89, 100-108.
27. Delint-Ramirez I, Fernandez E, Bayes A, Kicsi E, Komiyama NH, Grant SG (2010) In vivo composition of NMDA receptor signaling complexes differs between membrane subdomains and is modulated by PSD-95 and PSD-93. J Neurosci 30, 8162-8170.
28. Simons K, Ikonen E (2000) How cells handle cholesterol? Science 290, 1721-1726.
29. Farooqui AA, Horrocks LA (2007) Glycerophospholipids in the Brain: Phospholipases A2 in Neurological Disorders, Springer, New York.
30. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr., Morris JC (2001) Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology 56, 127-129.
31. Farooqui AA, Ong WY, Horrocks LA (2003) Plasmalogens, docosahexaenoic acid and neurological disorders. Adv Exp Med Biol 544, 335-354.
32. Farooqui T, Farooqui AA(2009) Aging: An important factor for the pathogenesis of neurodegenerative diseases. Mech Ageing Dev 130, 203-215.
33. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 30, 572-580.
34. De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP, Viola KL, Zhao WQ, Ferreira ST, Klein WL (2009) Protection of synapses against Alzheimer'slinked toxins: Insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A 106, 1971-1976.
35. Farooqui AA, Ong WY, Horrocks LA (2003) Stimulation of lipases and phospholipases in Alzheimer disease. In Nutrition and Biochemistry of Phospholipids, Szuhaj B, van Nieuwenhuyzen W, eds. AOCS Press, Champaign, pp. 14-29.
36. Parson CG, Stoffler A, Danysz W (2007) Memantine: A NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system-too little activation is bad, too much is even worse. Neuropharmacol 53, 699-723.
37. Putcha D, Brickhouse M, O'Keefe K, Sullivan C, Rentz D, Marshall G, Dickerson B, Sperling R (2011) Hippocampal hyperactivation associated with cortical thinning in Alzheimer's disease signature regions in non-demented elderly adults. J Neurosci 31, 17680-17688.
38. Sperling RA, Dickerson BC, Pihlajamaki M, Vannini P, LaViolette PS, Vitolo OV, Hedden T, Becker JA, Rentz DM, Selkoe DJ, Johnson KA (2010) Functional alterations in memory networks in early Alzheimer's disease. Neuromolecular Med 12, 27-43.
39. Fayed N, Modrego PJ, Rojas-Salinas G, Aguilar K (2011) Brain glutamate levels are decreased in Alzheimer's disease: A magnetic resonance spectroscopy study. Am J Alzheimers Dis Other Demen 26, 450-456.
40. Hoe HS, Fu Z, Makarova A, Lee JY, Lu C, Feng L, Pajoohesh-Ganji A, Matsuoka Y, Hyman BT, Ehlers MD, Vicini S, Pak DT, Rebeck GW(2009) The effects of amyloid precursor protein on postsynaptic composition and activity. J Biol Chem 284, 8495-8506.
41. Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ, Roberts BR, Volitakis I, Egan GF, McLean CA, Cappai R, Duce JA, Bush AI (2012) Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med 18, 291-295.
42. Sandbrink R, Masters CL, Beyreuther K (1996) APP gene family. Alternative splicing generates functionally related isoforms. Ann NY Acad Sci 777, 281-287.
43. LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci 8, 499-509.
44. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8, 101-112.
45. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 46, 860-866.
46. Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL (2004) Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci 24, 10191-10200.
47. De Felice FG, Wu D, Lambert MP, Fernandez SJ, Velasco PT, Lacor PN, Bigio EH, Jerecic J, Acton PJ, Shughrue PJ, Chen-Dodson E, Kinney GG, KleinWL(2008) Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A beta oligomers. Neurobiol Aging 29, 1334-1347.
48. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539.
49. Roselli F, Tirard M, Lu J, Hutzier P, Lamberti P, Livrea P, Morabito MK, Almeida OF (2005) Soluble betaamyloid1- 40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses. J Neurosci 25, 11061-11070.
50. Ke YD, Suchowerska AK, van der Hoven J, De Silva DM, Wu CW, van Eersel J, Ittner A, Ittner LM (2012) Lessons from tau-deficient mice. Int J Alzheimers Dis 2012, 1-8.
51. Alonso AC, Grundke-Iqbal I, Iqbal K (1996) Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 2, 783-787.
52. Stokin GB, Goldstein SB (2006) Axonal transport and Alzheimer's disease. Ann Rev Biochem 75, 607-627.
53. Ittner LM, Gotz J (2011) Amyloid-beta and tau-a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci 12, 67-72.
54. Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A (2002) Tau is essential to beta-amyloid-induced neurotoxicity. Proc Natl Acad Sci U S A 99, 6364-6369.
55. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 316, 750-754.
56. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J,Wölfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 142, 387-397.
57. Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, Rönicke R, Reymann K, Hutter-Paier B, Alexandru A, JaglaW, Graubner S, Glabe CG, Demuth HU, Bloom GS (2012) Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid. Nature 485, 651-655.
58. Huang Y (2006) Apolipoprotein E and Alzheimer disease. Neurology 66, S79-S85.
59. Mahley RW,Weisgraber KH, Huang Y (2006) Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci U S A 103, 5644-5651.
60. Bullido MJ, Artiga MJ, Recuero M, Sastre I, García MA, Aldudo J, Lendon C, HanSW,Morris JC, Frank A, Vázquez J, Goate A, Valdivieso F (1998) A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia. Nat Genet 18, 69-71.
61. Laws SM, Hone E, Gandy S, Martins RN (2003) Expanding the association between the APOE gene and the risk of Alzheimer's disease: Possible roles for APOE promoter polymorphisms and alterations in APOE transcription. J Neurochem 84, 1215-1236.
62. Bales KR, Verina T, Cummins DJ, Du Y, Dodel RC, Saura J, Fishman CE, DeLong CA, Piccardo P, Petegnief V, Ghetti B, PaulSM(1999) Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 96, 15233-15238.
63. Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM (2000) Apolipoprotein E isoformdependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 97, 2892-2897.
64. Cho HS, Hyman BT, Greenberg SM, Rebeck GW (2001) Quantitation of apoE domains in Alzheimer disease brain suggests a role for apoE in Abeta aggregation. J Neuropathol Exp Neurol 60, 342-349.
65. Gibson GE, HaroutunianV, Zhang H, Park LC, Shi Q, Lesser M, Mohs RC, Sheu RK, Blass JP (2000) Mitochondrial damage in Alzheimer's disease varies with apolipoprotein E genotype. Ann Neurol 48, 297-303.
66. Chang S, ran Ma T, Miranda RD, Balestra ME, Mahley RW, Huang Y (2005) Lipid-and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity. Proc Natl Acad Sci U S A 102, 18694-18699.
67. Chen HK, Ji ZS, Dodson SE, Miranda RD, Rosenblum CI, Reynolds IJ, Freedman SB, Weisgraber KH, Huang Y, Mahley RW (2011) Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease. J Biol Chem 286, 5215-5221.
68. Lee YJ, Choi IS, Park MH, Lee YM, Song JK, Kim YH, Kim KH, Hwang DY, Jeong JH, Yun YP, Oh KW, Jung JK, Han SB, Hong JT (2011) 4-O-Methylhonokiol attenuates memory impairment in presenilin 2 mutant mice through reduction of oxidative damage and inactivation of astrocytes and the ERK pathway. Free Radic Biol Med 50, 66-77.
69. Hardy J (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 20, 154-159.
70. Amtul Z, Lewis PA, Piper S, Crook R, Baker M, Findlay K, Singleton A, Hogg M, Younkin L, Younkin SG, Hardy J, Hutton M, Boeve BF, Tang-Wai D, Golde TE (2002) A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch. Neurobiol Dis 9, 269-273.
71. Lesné S, Ali C, Gabriel C, Croci N, MacKenzie ET, Glabe CG, Plotkine M, Marchand-Verrecchia C,Vivien D, Buisson A(2005)NMDAreceptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta production. J Neurosci 25, 9367-9377.
72. Brorson JR, Bindokas VP, Iwama T, Marcuccilli CJ, Chisholm JC, Miller RJ (1995) The Ca2+ influx induced by beta-amyloid peptide 25-35 in cultured hippocampal neurons results from network excitation. J Neurobiol 26, 325-338.
73. Fu W, Ruangkittisakul A, MacTavish D, Shi JY, Ballanyi K, Jhamandas JH (2012) Amyloid-(A) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways. J Biol Chem 287, 18820-18830.
74. Bobich JA, Zheng Q, Campbell A(2004) Incubation of nerve endings with a physiological concentration of Abeta1-42 activates CaV2.2(N-Type)-voltage operated calcium channels and acutely increases glutamate and noradrenaline release. J Alzheimers Dis 6, 243-255.
75. Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci 31, 454-463.
76. Camandola S, Mattson MP(2011) Aberrant subcellular neuronal calcium regulation in aging and Alzheimer's disease. Biochim Biophys Acta 1813, 965-973.
77. He Y, Cui J, Lee JC, Ding S, Chalimoniuk M, Simonyi A, Sun AY, Gu Z, Weisman GA, Wood WG, Sun GY (2011) Prolonged exposure of cortical neurons to oligomeric amyloid-impairs NMDA receptor function via NADPH oxidase-mediated ROS production: Protective effect of green tea (-)-epigallocatechin-3-gallate. ASN Neuro 3, e00050.
78. Wu J, Anwyl R, Rowan MJ (1995) beta Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. Neuroreport 6, 2409-2413.
79. Ferreira IL, Resende R, Ferreiro E, Rego AC, Pereira CF (2010) Multiple defects in energy metabolism in Alzheimer's disease. Curr Drug Targets 11, 1193-1206.
80. Tominaga-Yoshino K, Uetsuki T, Yoshikawa K, Ogura A (2001) Neurotoxic and neuroprotective effects of glutamate are enhanced by introduction of amyloid precursor protein cDNA. Brain Res 918, 121-130.
81. Costa RO, Lacor PN, Ferreira IL, Resende R, Auberson YP, Klein WL, Oliveira CR, Rego AC, Pereira CM(2012) Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-d-aspartate receptor in mature hippocampal cultures treated with amyloid-oligomers. Aging Cell 11, 823-833.
82. Wu S, Basile AS, Barger SW (2007) Induction of serine racemase expression and D-serine release from microglia by secreted amyloid precursor protein (sAPP). Curr Alzheimer Res 4, 243-251.
83. Fernandez-Tome P, Brera B, Arevalo MA, de Ceballos ML (2004) Beta-amyloid25-35 inhibits glutamate uptake in cultured neurons and astrocytes: Modulation of uptake as a survival mechanism. Neurobiol Dis 15, 580-589.
84. Matos M, Augusto E, Oliveira CR, Agostinho P (2008) Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: Involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience 156, 898-910.
85. Liang Z, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX (2009) Dysregulation of tau phosphorylation in mouse brain during excitotoxic damage. J Alzheimers Dis 17, 531-539.
86. Suzuki T, Okumura-Noji K (1995) NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain. Biochem Biophys Res Commun 216, 582-588.
87. Götz J, Ittner A, Ittner LM (2012) Tau-targeted treatment strategies in Alzheimer's disease. Br J Pharmacol 165, 1246-1259.
88. Boimel M, Grigoriadis N, Lourbopoulos A, Haber E, Abramsky O, Rosenmann H (2010) Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice. Exp Neurol 224, 472-485.
89. Wisniewski T, Sigurdsson EM (2010) Murine models of Alzheimer's disease and their use in developing immunotherapies. Biochim Biophys Acta 1802, 847-859.
90. Aono M, Lee Y, Grant ER, Zivin RA, Pearlstein RD,Warner DS, Bennett ER, Laskowitz DT (2002) Apolipoprotein E protects against NMDA excitotoxicity. Neurobiol Dis 11, 214-220.
91. Lee Y, Aono M, Laskowitz D, Warner DS, Pearlstein RD (2004) Apolipoprotein E protects against oxidative stress in mixed neuronal-glial cell cultures by reducing glutamate toxicity. Neurochem Int 44, 107-118.
92. Ong WY, He Y, Suresh S, Patel SC (1997) Differential expression of apolipoprotein D and apolipoprotein E in the kainic acid-lesioned rat hippocampus. Neuroscience 79, 359-367.
93. Buttini M, Masliah E, Yu GQ, Palop JJ, Chang S, Bernardo A, Lin C,Wyss-Coray T, Huang Y, Mucke L (2010) Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice. Am J Pathol 177, 563-569.
94. Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S,Wu HM,Mega MS, Cummings JL, Saunders AM,Pericak-Vance MA,Roses AD, Barrio JR, Phelps ME (2000) Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A 97, 6037-6042.
95. Grilli M, Diodato E, Lozza G, Brusa R, Casarini M, Uberti D, Rozmahel R, Westaway D, St George-Hyslop P, Memo M, Ongini E (2000) Presenilin-1 regulates the neuronal threshold to excitotoxicity both physiologically and pathologically. Proc Natl Acad Sci U S A 97, 12822-12827.
96. Schulte EC, Slawik H, Schüle R, Gunther T, Hüll M (2009) Alterations in excitotoxicity and prostaglandin metabolism in a transgenic mouse model of Alzheimer's disease. Neurochem Int 55, 689-696.
97. Widner B, Leblhuber F, Walli J, Tilz GP, Demel U, Fuchs D (2000) Tryptophan degradation and immune activation in Alzheimer's disease. J Neural Transm 107, 343-353.
98. Porter RJ, Lunn BS, O'Brien JT (2003) Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly. Psychol Med 33, 41-49.
99. Rahman A, Ting K, Cullen KM, Braidy N, Brew BJ, Guillemin GJ (2009) The excitotoxin quinolinic acid induces tau phosphorylation in human neurons. PLoS One 4, e6344.
100. Oda T, Pasinetti GM, Osterburg HH, Anderson C, Johnson SA, Finch CE (1994) Purification and characterization of brain clusterin. Biochem Biophys Res Commun 204, 1131-1136.
101. Boggs LN, Fuson KS, Baez M, Churgay L, McClure D, Becker G, May PC (1996) Clusterin (Apo J) protects against in vitro amyloid-beta (1-40) neurotoxicity. J Neurochem 67, 1324-1327.
102. Matsubara E, Soto C, Governale S, Frangione B, Ghiso J (1996) Apolipoprotein J and Alzheimer's amyloid beta solubility. Biochem J 316, 671-679.
103. Ghiso J, Matsubara E,Koudinov A, Choi-Miura NH, Tomita M, Wisniewski T, Frangione B (1993) The cerebrospinalfluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex. Biochem J 293, 27-30.
104. Frippiat C, Chen QM, Zdanov S, Magalhaes JP, Remacle J, Toussaint O (2001) Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts. J Biol Chem 276, 2531-2537.
105. Shin YJ, Kim JH, Seo JM, Lee SM, Hyon JY, Yu YS, Wee WR(2009) Protective effect of clusterin on oxidative stressinduced cell death of human corneal endothelial cells. Mol Vis 15, 2789-2795.
106. Kim JH, Kim JH, Jun HO, Yu YS, Min BH, Park KH, Kim KW(2010) Protective effect of clusterin from oxidative stress-induced apoptosis in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 51, 561-566.
107. Zhang H, Kim JK, Edwards CA, Xu Z, Taichman R, Wang CY (2005) Clusterin inhibits apoptosis by interacting with activated Bax. Nat Cell Biol 7, 909-915.
108. Trougakos IP, Lourda M, Antonelou MH, Kletsas D, Gorgoulis VG, Papassideri IS, Zou Y, Margaritis LH, Boothman DA, Gonos ES (2009) Intracellular clusterin inhibits mitochondrial apoptosis by suppressing p53-activating stress signals and stabilizing the cytosolic Ku70-Bax protein complex. Clin Cancer Res 15, 48-59.
109. Xiao Q, Gil SC, Yan P, Wang Y, Han S, Gonzales E, Perez R, Cirrito JR, Lee JM (2012) Role of phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) in intracellular amyloid precursor protein (APP) processing and amyloid plaque pathogenesis. J Biol Chem 287, 21279-21289.
110. Baig S, Joseph SA, Tayler H, Abraham R, Owen MJ, Williams J, Kehoe PG, Love S (2010) Distribution and expression of picalm in Alzheimer disease. J Neuropathol Exp Neurol 69, 1071-1077.
111. Harel A, Wu F, Mattson MP, Morris CM, Yao PJ (2008) Evidence forCALMin directingVAMP2 trafficking. Traffic 9, 417-429.
112. Klebig ML, Wall MD, Potter MD, Rowe EL, Carpenter DA, Rinchik EM (2003) Mutations in the clathrin-assembly gene Picalm are responsible for the hematopoietic and iron metabolism abnormalities in fit1 mice. Proc Natl Acad Sci U S A 100, 8360-8365.
113. Treusch S, Hamamichi S, Goodman JL, Matlack KE, Chung CY, BaruV, Shulman JM, Parrado A, Bevis BJ,Valastyan JS, Han H, Lindhagen-Persson M, Reiman EM, EvansDA, Bennett DA, Olofsson A, DeJager PL, Tanzi RE, Caldwell KA, Caldwell GA, Lindquist S (2011) Functional links between A-toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast. Science 334, 1241-1245.
114. D'Angelo F, Vignaud H, Di Martino J, Salin B, Devin A, Cullin C, Marchal C (2013) A yeast model for amyloid-aggregation exemplifies the role of membrane trafficking and PICALM in cytotoxicity. Dis Model Mech 6, 206-216.
115. Rudinskiy N, Grishchuk Y, Vaslin A, Puyal J, Delacourte A, Hirling H, Clarke PG, Luthi-Carter R (2009) Calpain hydrolysis of alpha-and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration. J Biol Chem 284, 12447-12458.
116. McGreal E, Gasque P (2002) Structure-function studies of the receptors for complement C1q. Biochem Soc Trans 30, 1010-1014.
117. Ten VS, Yao J, Ratner V, Sosunov S, Fraser DA, Botto M, Sivasankar B, Morgan BP, Silverstein S, Stark R, Polin R, Vannucci SJ, Pinsky D, Starkov AA (2010) Complement component c1q mediates mitochondria-driven oxidative stress in neonatal hypoxic-ischemic brain injury. J Neurosci 30, 2077-2087.
118. Gao LJ, Gu PQ, Fan WM, Liu Z, Qiu F, Peng YZ, Guo XR (2011) The role of gC1qR in regulating survival of human papillomavirus 16 oncogene-transfected cervical cancer cells. Int J Oncol 39, 1265-1272.
119. McGee AM, Baines CP (2011) Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J 433, 119-125.
120. Chu Y, Jin X, Parada I, Pesic A, Stevens B, Barres B, Prince DA (2010) Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc Natl Acad Sci U S A 107, 7975-7980.
121. Di Paolo G, Sankaranarayanan S, Wenk MR, Daniell L, Perucco E, Caldarone BJ, Flavell R, Picciotto MR, Ryan TA, Cremona O, De Camilli P (2002) Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33, 789-804.
122. Kim WS, Fitzgerald ML, Kang K, Okuhira K, Bell SA, Manning JJ, Koehn SL, Lu N, Moore KJ, Freeman MW (2005) Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels. J Biol Chem 280, 3989-3995.
123. Jehle AW, Gardai SJ, Li S, Linsel-Nitschke P, Morimoto K, Janssen WJ,Vandivier RW,Wang N, Greenberg S, Dale BM, Qin C, Henson PM, Tall AR (2006) ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. J Cell Biol 174, 547-556.
124. Liang Y, Buckley TR, Tu L, Langdon SD, Tedder TF (2001) Structural organization of the human MS4A gene cluster on Chromosome 11q12. Immunogenetics 53, 357-368.
125. Koslowski M, Sahin U, Dhaene K, Huber C, Türeci O(2008) MS4A12 is a colon-selective store-operated calcium channel promoting malignant cell processes. Cancer Res 68, 3458-3466.
126. Cormont M, Metón I, Mari M, Monzo P,Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y (2003) CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl. Traffic 4, 97-112.
127. Carter C (2011) Alzheimer's disease: APP, gamma secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and their relationships with herpes simplex, C. pneumoniae, other suspect pathogens, and the immune system. Int J Alzheimers Dis 2011, 501862.
128. von Gunten S, Yousefi S, Seitz M, Jakob SM, Schaffner T, Seger R, Takala J, Villiger PM, Simon HU (2005) Siglec-9 transduces apoptotic and non-apoptotic death signals into neutrophils depending on the pro-inflammatory cytokine environment. Blood 106, 1423-1431.
129. von Gunten S, Simon HU (2006) Sialic acid binding immunoglobulin-like lectins may regulate innate immune responses by modulating the life span of granulocytes. FASEB J 20, 601-605.
130. Nutku E, Hudson SA, Bochner BS (2005) Mechanism of Siglec-8-induced human eosinophil apoptosis: Role of caspases and mitochondrial injury. Biochem Biophys Res Commun 336, 918-924.
131. Cissé M, Halabisky B, Harris J, Devidze N, Dubal DB, Sun B, Orr A, Lotz G, Kim DH, Hamto P, Ho K,Yu GQ, Mucke L (2011) Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 469, 47-52.
132. Sloniowski S, Ethell IM (2012) Looking forward to EphB signaling in synapses. Semin Cell Dev Biol 23, 75-82.
133. Barthet G, Dunys J, Shao Z, Xuan Z, Ren Y, Xu J, Arbez N, Mauger G, Bruban J, Georgakopoulos A, Shioi J, Robakis NK (2013) Presenilin mediates neuroprotective functions of ephrinB and brain-derived neurotrophic factor and regulates ligand-induced internalization and metabolism of EphB2 and TrkB receptors. Neurobiol Aging 34, 499-510.
134. de la Monte SM, Wands JR (2008) Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2, 1101-1113.
135. Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE (2012) Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122, 1316-1338.
136. Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel JC, Decker H, Silverman MA, Kazi H, Melo HM, McClean PL, Holscher C, Arnold SE, Talbot K, Klein WL, Munoz DP, Munoz DP, De Felice FG (2012) An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated A-oligomers. J Clin Invest 122, 1339-1353.
137. Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM (2009) Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: Suppression by omega-3 fatty acids and curcumin. J Neurosci 29, 9078-9089.
138. Farooqui AA, Farooqui T, Panza F, Frisardi V (2012) Metabolic syndrome as a risk factor for neurological disorders. Cell Mol Life Sci 69, 741-762.
139. Camacho A, Montiel T, Massieu L (2007) Sustained metabolic inhibition induces an increase in the content and phosphorylation of the NR2B subunit of N-methyl-Daspartate receptors and a decrease in glutamate transport in the rat hippocampus in vivo. Neuroscience 145, 873-886.
140. Bennett RG, Duckworth WC, Hamel FG (2000) Degradation of amylin by insulin-degrading enzyme. J Biol Chem 275, 36621-36625.
141. Kurochkin IV (2001) Insulin-degrading enzyme: Embarking on amyloid destruction. Trends Biochem Sci 26, 421-425.
142. Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, Roth RA, Schellenberg GD, Jin LW, Kovacina KS, Craft S (2003) Reduced hippocampal insulin-degrading enzyme in lateonset Alzheimer's disease is associated with the apolipoprotein Eepsilon4 allele. Am J Pathol 162, 313-319.
143. de la Monte SM (2012) Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer's disease. Drugs 72, 49-66.
144. Ke YD, Delerue F, Gladbach A, Gotz J, Ittner LM (2009) Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer's disease. PLoS One 4, e7917.
145. Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100, 4162-4167.
146. Bosco D, Fava A, Plastino M, Montaecini T, Puja A (2011) Possible implications of insulin resistance and glucose metabolism in Alzheimer's disease pathogenesis. J Cell Mol Med 15, 1807-1821.
147. Yamagishi S, Nakamura K, Inoue H, Kikuchi S, Takeuchi M (2005) Serum or cerebrospinal fluid levels of glyceraldehyde-derived advanced glycation end products (AGEs) may be a promising biomarker for early detection of Alzheimer's disease. Med Hypotheses 64, 1205-1207.
148. Kilbride SM, Gluchowska SA, Telford JE, O'Sullivan C, Davey GP (2011) High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal. Mol Neurodegener 26, 53.
149. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 304, 448-452.
150. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15, 1437-1449.
151. Dumont M, Beal MF (2011) Neuroprotective strategies involving ROS in Alzheimer disease. Free Radic Biol Med 51, 1014-1026.
152. Farooqui AA (2011) Lipid Mediators and their Metabolism in the Brain, Springer, New York.
153. Lieb W, Beiser AS, Vasan RS, Tan ZS, Au R, Harris TB, Roubenoff R, Auerbach S, DeCarli C, Wolf PA, Seshadri S (2009) Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. JAMA 302, 2565-2572.
154. Tezapsidis N, Johnston JM, Smith MA, Ashford JW, Casadesus G, Robakis NK, Wolozin B, Perry G, Zhu X, Greco SJ, Sarkar S (2009) Leptin: A novel therapeutic strategy for Alzheimer's disease. J Alzheimers Dis 16, 731-740.
155. Shanley LJ, Irving AJ, Harvey J (2001) Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity. J Neurosci 21, RC186.
156. OomuraY, Hori N, Shiraishi T, FukunagaK, Takeda H, Tsuji M, Matsumiya T, Ishibashi M, Aou S, Li XL (2006) Leptin facilitates learning and memory performance and enhances hippocampalCA1longterm potentiation andCaMKII phosphorylation in rats. Peptides 27, 2738-2749.
157. Fewlass DC, Noboa K, Pi-Sunyer FX, Johnston JM, Yan SD, Tezapsidis N (2004) Obesity-related leptin regulates Alzheimer's Abeta. FASEB J 18, 1870-1878.
158. Greco SJ, Bryan KJ, Sarkar S, Zhu X, Smith MA, Ashford JW, Johnston JM, Tezapsidis N, Casadesus G (2010) Chronic leptin supplementation ameliorates pathology and improves cognitive performance in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 19, 1155-1167.
159. Beccano-Kelly D, Harvey J (2012) Leptin: A novel therapeutic target in Alzheimer's disease? Int J Alzheimers Dis 2012, 594137.
160. Pichika R, Taha AY, Gao F, Kotta K, Cheon Y, Chang L, Kiesewetter D, Rapoport SI, Eckelman WC (2012) The synthesis and in vivo pharmacokinetics of fluorinated arachidonic acid: Implications for imaging neuroinflammation. J Nucl Med 53, 1383-1391.
161. Esposito G, Giovacchini G, Liow JS, Bhattacharjee AK, Greenstein D, Schapiro M, Hallett M, Herscovitch P, Eckelman WC, Carson RE, Rapoport SI (2008) Imaging neuroinflammation in Alzheimer's disease with radiolabeled arachidonic acid and PET. J Nucl Med 49, 1414-1421.
162. Kanfer JN, Sorrentino G, Sitar DS (1998) Phospholipases as mediators of amyloid beta peptide neurotoxicity: An early event contributing to neurodegeneration characteristic of Alzheimer's disease. Neurosci Lett 257, 93-96.
163. Sanchez-Mejia RO, Newman JW, Toh S, Yu GQ, Zhou Y, Halabisky B, Cissé M, Scearce-Levie K, Cheng IH, Gan L, Palop JJ, Bonventre JV, Mucke L (2008) Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nat Neurosci 11, 1311-1318.
164. Ong WY, Sandhya TL, Horrocks LA, Farooqui AA (1999) Distribution of cytoplasmic phospholipase A2 in the normal rat brain. J Hirnforsch 39, 391-400.
165. Ong WY, Lu XR, Ong BK, Horrocks LA, Farooqui AA, Lim SK (2003) Quinacrine abolishes increases in cytoplasmic phospholipaseA2 mRNAlevels in the rat hippocampus after kainate-induced neuronal injury. Exp Brain Res 148, 521-524.
166. Sandhya TL, Ong WY, Horrocks LA, Farooqui AA (1998) A light and electron microscopic study of cytoplasmic phospholipase A2 and cyclooxygenase-2 in the hippocampus after kainate lesions. Brain Res 788, 223-231.
167. Ong WY, Lu XR, Hu CY, Halliwell B (2000) Distribution of hydroxynonenal-modified proteins in the kainate-lesioned rat hippocampus: Evidence that hydroxynonenal formation precedes neuronal cell death. Free Radic Biol Med 28, 1214-1221.
168. Lu XR, Ong WY, Halliwell B, Horrocks LA, Farooqui AA (2001) Differential effects of calcium-dependent and calcium-independent phospholipase A(2) inhibitors on kainate-induced neuronal injury in rat hippocampal slices. Free Radic Biol Med 30, 1263-1273.
169. Moses GS, Jensen MD, Lue LF, Walker DG, Sun AY, Simonyi A, Sun GY (2006) Secretory PLA2-IIA: A new inflammatory factor for Alzheimer's disease. J Neuroinflammation, 3, 28.
170. Jensen MD, Sheng W, Simonyi A, Johnson GS, Sun AY, Sun GY (2009) Involvement of oxidative pathways in cytokine-induced secretory phospholipase A2-IIA in astrocytes. Neurochem Int 55, 362-368.
171. Thwin MM, Ong WY, Fong CW, Sato K, Kodama K, Farooqui AA, Gopalakrishnakone P (2003) Secretory phospholipase A2 activity in the normal and kainate injected rat brain, and inhibition by a peptide derived from python serum. Exp Brain Res 150, 427-433.
172. Than A, Tan Y, Ong WY, Farooqui AA, Chen P (2012) Kainate receptors mediate regulated exocytosis of secretory phospholipase A(2) in SH-SY5Y neuroblastoma cells. Neurosignals 20, 72-85.
173. Wei S, Ong WY, Thwin MM, Fong CW, Farooqui AA, Gopalakrishnakone P, Hong W (2003) Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons. Neuroscience 121, 891-898.
174. Yang X, ShengW, He Y, Cui J, Haidekker MA, Sun GY, Lee JC (2010) Secretory phospholipase A2 type III enhances alpha-secretase-dependent amyloid precursor protein processing through alterations in membrane fluidity. J Lipid Res 51, 957-966.
175. Zhu D, Lai Y, Shelat PB, Hu C, Sun GY, Lee JC (2006) Phospholipases A2 mediate amyloid-beta peptide-induced mitochondrial dysfunction. J Neurosci 26, 11111-11119.
176. Lee JC, Simonyi A, Sun AY, Sun GY (2009) Phospholipases A2 and neural membrane dynamics: Implications for Alzheimer's disease. J Neurochem 116, 813-819.
177. Shelat PB, Chalimoniuk M,Wang JH, Strosznajder JB, Lee JC, Sun AY, Simonyi A, Sun GY (2008) Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipaseA2 in cortical neurons. J Neurochem 106, 45-55.
178. Zhu D, Hu C, Sheng W, Tan KS, Haidekker MA, Sun AY, Sun GY, Lee JC (2009) NAD(P)H oxidase-mediated reactive oxygen species production alters astrocyte membrane molecular order via phospholipase A2. Biochem J 421, 201-210.
179. Askarova S, Yang X, Sheng W, Sun GY, Lee JC (2011) Role of A-receptor for advanced glycation endproducts interaction in oxidative stress and cytosolic phospholipase A2 activation in astrocytes and cerebral endothelial cells. Neuroscience 199, 375-385.
180. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11, 81-128.
181. Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP (1997) A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem 68, 255-264.
182. Keller JN, Mark RJ, Bruce AJ, Blanc E, Rothstein JD, Uchida K,Waeg G, Mattson MP (1997) 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience 80, 685-696.
183. Choi SH, Aid S, Caracciolo L, Sakura Minami S, Niikura T, Matsuoka Y, Turner RS, Mattson MP, Bosetti F (2013) Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease. J Neurochem 124, 59-68.
184. Farooqui AA (2009) Hot Topics in Neural Membrane Lipidology, Springer, New York.
185. Farooqui AA, Horrocks LA (2007) Glycerophospholipids in Brain: Phospholipase A2 in Neurological Disorders, Springer, New York.
186. Ma MT, Yeo JF, Farooqui AA, Zhang J, Chen P, Ong WY (2010) Differential effects of lysophospholipids on exocytosis in rat PC12 cells. J Neural Transm 117, 301-308.
187. Talbot K, Young RA, Jolly-Tornetta C, Lee VM, Trojanowski JQ,Wolf BA(2000)Afrontal variant of Alzheimer's disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex. Neurochem Int 37, 17-31.
188. Gattaz WF, Forlenza OV,Talib LL, Barbosa NR, Bottino CM (2004) Platelet phospholipase A(2) activity in Alzheimer's disease and mild cognitive impairment. J Neural Transm 111, 591-601.
189. Ong WY, Farooqui T, Farooqui AA (2010) Involvement of cytosolic phospholipase A(2), calcium independent phospholipase A(2) and plasmalogen selective phospholipase A(2) in neurodegenerative and neuropsychiatric conditions. Curr Med Chem 17, 2746-2763.
190. Dyall SC, Michael GJ, Whelpton R, Scott AG, Michael-Titus AT (2007) Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrain. Neurobiol Aging 28, 424-439.
191. Ménard C, Patenaude C, Gagné AM, Massicotte G (2009) AMPA receptor-mediated cell death is reduced by docosahexaenoic acid but not by eicosapentaenoic acid in area CA1 of hippocampal slice cultures. J Neurosci Res 87, 876-886.
192. Bazan NG, Musto AE, Knott EJ (2011) Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity. Mol Neurobiol 44, 216-222.
193. Allyson J, Bi X, Baudry M, Massicotte G (2012) Maintenance of synaptic stability requires calcium-independent phospholipase A2 activity. Neural Plast 2012, 569149.
194. Kuo YM, Emmerling MR, Bisgaier CL, Essenburg AD, Lampert HC, Drumm D, Roher AE (1998) Elevated lowdensity lipoprotein in Alzheimer's disease correlates with brain abeta 1-42 levels. Biochem Biophys Res Commun 252, 711-715.
195. Lazar AN, Bich C, Panchal M, Desbenoit N, Petit VW, Touboul D, Dauphinot L, Marquer C, Laprévote O, Brunelle A, Duyckaerts C (2013) Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients. Acta Neuropathol 125, 133-144.
196. Prasanthi JR, Huls A, Thomasson S, Thompson A, Schommer E, Ghribi O (2009) Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on betaamyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol Neurodegener 4, 1.
197. Barrett PJ, Song Y, Van Horn WD, Hustedt EJ, Schafer JM, Hadziselimovic A, Beel AJ, Sanders CR(2012) The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science 336, 1168-1171.
198. Chen P, Shen A, Zhao W, Baek SJ, Yuan H, Hu J (2009) Raman signature from brain hippocampus could aid Alzheimer's disease diagnosis. Appl Opt 48, 4743-4748.
199. Ong WY,Goh EW,Lu XR, Farooqui AA, Patel SC, Halliwell B (2003) Increase in cholesterol and cholesterol oxidation products, and role of cholesterol oxidation products in kainate-induced neuronal injury. Brain Pathol 13, 250-262.
200. He X, Jenner AM, Ong WY, Farooqui AA, Patel SC (2006) Lovastatin modulates increased cholesterol and oxysterol levels and has a neuroprotective effect on rat hippocampal neurons after kainate injury. J Neuropathol Exp Neurol 65, 652-663.
201. Kim JH, Jittiwat J, Ong WY, Farooqui AA, Jenner AM (2010) Changes in cholesterol biosynthetic and transport pathways after excitotoxicity. J Neurochem 112, 34-41.
202. Ong WY, Kim JH, He X, Chen P, Farooqui AA, Jenner AM (2010) Changes in brain cholesterol metabolome after excitotoxicity. Mol Neurobiol 41, 299-313.
203. Wolozin B (2004) Cholesterol and the biology of Alzheimer's disease. Neuron 41, 7-10.
204. Fantini J, Yahi N (2010) Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: Common mechanisms in neurodegenerative diseases. Expert Rev Mol Med 12, e27.
205. Zhang J, Xue R, Ong WY, Chen P (2009) Roles of cholesterol in vesicle fusion and motion. Biophys J 97, 1371-1380.
206. Nelson TJ, Alkon DL (2005) Oxidation of cholesterol by amyloid precursor protein and beta-amyloid peptide. J Biol Chem 280, 7377-7387.
207. Berthier A, Lemaire-Ewing S, Prunet C, Montange T, Vejux A, Pais de Barros JP, Monier S, Gambert P, Lizard G, Néel D (2005) 7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent transduction pathways. FEBS J 272, 3093-3104.
208. Han JH, Kim YJ, Han ES, Lee CS (2007) Prevention of 7-ketocholesterol- induced mitochondrial damage and cell death by calmodulin inhibition. Brain Res 1137, 11-19.
209. Luthra S, Dong J, Gramajo AL, Chwa M, Kim DW, Neekhra A, Kuppermann BD, Kenney MC (2008) 7-Ketocholesterol activates caspases-3/7,-8, and-12 in human microvascular endothelial cells in vitro. Microvasc Res 75, 343-350.
210. Ma MT, Zhang J, Farooqui AA, Chen P, Ong WY (2010) Effects of cholesterol oxidation products on exocytosis. Neurosci Lett 476, 36-41.
211. Haughey NJ, Bandaru VV, Bae M, Mattson MP(2010) Roles for dysfunctional sphingolipid metabolism in Alzheimer's disease neuropathogenesis. Biochim Biophys Acta 1801, 878-886.
212. Han X, Holtzman D, McKeel DW, Jr., Kelley J, Morris JC (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: Potential role in disease pathogenesis. J Neurochem 82, 809-818.
213. Cutler RG, Kelley J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci U S A 101, 2070-2075.
214. He X, Huang Y, Li B, Gong CX, Schuchman EH (2010) Deregulation of sphingolipid metabolism in Alzheimer's disease. Neurobiol Aging 31, 398-408.
215. Tong M, de la Monte SM (2009) Mechanisms of ceramide-mediated neurodegeneration. J Alzheimer Dis 16, 705-714.
216. Guan XL, He X, Ong WY, Yeo WK, Shui G, Wenk MR (2006) Non-targeted profiling of lipids during kainateinduced neuronal injury. FASEB J 20, 1152-1161.
217. He X, Guan XL, Ong WY, Farooqui AA, Wenk MR (2007) Expression, activity, and role of serine palmitoyltransferase in the rat hippocampus after kainate injury. J Neurosci Res 85, 423-432.
218. Tang N, Ong WY, Zhang EM, Chen P, Yeo JF (2007) Differential effects of ceramide species on exocytosis in rat PC12 cells. Exp Brain Res 183, 241-247.
219. Barry G, Ross IL (2008) Neurosteroids and sporadic Alzheimer's disease. Curr Alzheimer Res 5, 367-374.
220. Chia WJ, Jenner AM, Farooqui AA, Ong WY (2008) Changes in cytochrome P450 side chain cleavage expression in the rat hippocampus after kainate injury. Exp Brain Res 186, 143-149.
221. Mizuno T (2012) The biphasic role of microglia in Alzheimer's disease. Int J Alzheimers Dis 2012, 737846.
222. Rogove AD, Tsirka SE (1998) Neurotoxic responses by microglia elicited by excitotoxic injury in the mouse hippocampus. Curr Biol 8, 19-25.
223. Meda L, Cassatella MA, Szendrei GI, Otvos L Jr., Baron P, Villalba M, Ferrari D, Rossi F (1995) Activation of microglial cells by beta-amyloid protein and interferongamma. Nature 374, 647-650.
224. Halliwell B, Gutteridge JM (1997) Lipid peroxidation in brain homogenates: The role of iron and hydroxyl radicals. J Neurochem 69, 1330-1331.
225. Chao C, Hu S, Molitor T, Shaskan E, Peterson P (1992) Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol 149, 2736-2741.
226. Martínez-Ruiz A, Cadenas S, Lamas S (2011) Nitric oxide signaling: Classical, less classical and nonclassical mechanisms. Free Radic Biol Med 51, 17-29.
227. Abrams AJ, Farooq A, Wang G (2011) S-nitrosylation of ApoE in Alzheimer's disease. Biochemistry 50, 3405-3407.
228. Qin S, Colin C, Hinners I, Gervais A, Cheret C, Mallat M (2006) System Xc-and apolipoprotein E expressed by microglia have opposite effects on the neurotoxicity of amyloid-beta peptide 1-40. J Neurosci 26, 3345-3356.
229. Murugan M, Sivakumar V, Lu J, Ling EA, Kaur C (2011) Expression of N-methyl D-aspartate receptor subunits in amoeboid microglia mediates production of nitric oxide via NF-κB signaling pathway and oligodendrocyte cell death in hypoxic postnatal rats. Glia 59, 521-539.
230. Kaindl AM, Degos V, Peineau S, Gouadon E, Chhor V, Loron G, Le Charpentier T, Josserand J, Ali C, Vivien D, Collingridge GL, Lombet A, Issa L, Rene F, Loeffler JP, Kavelaars A, Verney C,Mantz J, Gressens P (2012) Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain. Ann Neurol 72, 536-549.
231. Steele ML, Robinson SR (2012) Reactive astrocytes give neurons less support: Implications for Alzheimer's disease. Neurobiol Aging 33, 423e1-42313.
232. Frederickson RC (1992) Astroglia in Alzheimer's disease. Neurobiol Aging 13, 239-253.
233. Matos M, Augusto E, Machado NJ, dos Santos-Rodrigues A, Cunha RA, Agostinho P (2012) Astrocytic adenosine A2A receptors control the amyloid-peptide-induced decrease of glutamate uptake. J Alzheimers Dis 31, 555-567.
234. Zhong N, Scearce-Levie K, Ramaswamy G, Weisgraber KH (2008) Apolipoprotein E4 domain interaction: Synaptic and cognitive deficits in mice. Alzheimers Dement 4, 179-192.
235. Smith MA, Harris PLR, Sayre LM, Perry G (1997) Iron accumulation in Alzheimer disease is a source of redoxgenerated free radicals. Proc Nat Acad Sci U S A 94, 9866-9868.
236. Piñero DJ, Hu J, Connor JR (2000) Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's diseased brains. Cell Mol Biol 46, 761-776.
237. Silvestri L, Camaschella C (2008) A potential pathogenetic role of iron in Alzheimer's disease. J Cell Mol Med 12, 1548-1550.
238. Egana JT, Zambrano C, Nunez MT, Gonzalez-Billault C, Maccioni RB (2003) Iron-induced oxidative stress modify tau phosphorylation patterns in hippocampal cell cultures. Biometals 16, 215-223.
239. Jomova K, Valko M (2011) Importance of iron chelation in free radical-induced oxidative stress and human disease. Curr Pharm Design 17, 3460-3473.
240. Butterfield DA, Bush AI (2004) Alzheimer's amyloid betapeptide (1-42): Involvement of methionine residue 35 in the oxidative stress and neurotoxicity properties of this peptide. Neurobiol Aging 25, 563-568.
241. Ong WY, Ren MQ, Makjanic J, Lim TM, Watt F (1999) A nuclear microscopic study of elemental changes in the rat hippocampus after kainate-induced neuronal injury. J Neurochem 72, 1574-1579.
242. Wang XS, Ong WY, Connor JR (2002) Increase in ferric and ferrous iron in the rat hippocampus with time after kainateinduced excitotoxic injury. Exp Brain Res 143, 137-148.
243. Huang E, Ong WY (2005) Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injury. Exp Brain Res 161, 502-511.
244. Wang XS, Ong WY, Connor JR (2002) A light and electron microscopic study of divalent metal transporter-1 distribution in the rat hippocampus, after kainate-induced neuronal injury. Exp Neurol 177, 193-201.
245. Huang E, Ong WY, Go ML, Connor JR (2006) Upregulation of iron regulatory proteins and divalent metal transporter-1 isoforms in the rat hippocampus after kainate induced neuronal injury. Exp Brain Res 170, 376-386.
246. Chen JH, Shahnavas S, Singh N, Ong WY,Walczyk T(2013) Stable iron isotope tracing reveals significant brain iron uptake in adult rats. Metallomics 5, 167-173.
247. Ong WY, Tan B, Pan N, Jenner A, Whiteman M, Ong CN, Watt F, Halliwell B (2004) Increased iron staining in the cerebral cortex of cholesterol fed rabbits. Mech Ageing Dev 125, 305-313.
248. Ong WY, Jenner AM, Pan N, Ong CN, Halliwell B (2009) Elevated oxidative stress, iron accumulation around microvessels and increased 4-hydroxynonenal immunostaining in zone 1 of the liver acinus in hypercholesterolemic rabbits. Free Radic Res 43, 241-249.
249. Ong WY, Halliwell B (2004) Iron, atherosclerosis, and neurodegeneration: A key role for cholesterol in promoting iron-dependent oxidative damage? Ann N Y Acad Sci 1012, 51-64.
250. Ong WY, Ong BKC, Farooqui AA, Chiueh CC, Connor JR (2003) Iron and epilepsy. In Metal Ions and Neurodegenerative Disorders. Zatta P, ed. World Scientific, Singapore. pp. 365-398.
251. Lipton SA (2007) Pathologically activated therapeutics for neuroprotection. Nat Rev Neurosci 8, 803-808.
252. Burke D (2012) Donepezil or memantine improved cognitive functioning in moderate-to-severe Alzheimer disease. Ann Intern Med 156, JC6-J10.
253. Annweiler C, Beauchet O (2012) Possibility of a new anti-Alzheimer's disease pharmaceutical composition combining memantine and vitamin D. Drugs Aging 29, 81-91.
254. Seki M, Lipton SA (2008) Targeting excitotoxic/free radical signaling pathways for therapeutic intervention in glaucoma. Prog Brain Res 173, 495-510.
255. Song MS, Rauw G, Baker GB, Kar S (2008) Memantine protects rat cortical cultured neurons against beta-amyloidinduced toxicity by attenuating tau phosphorylation. Eur J Neurosci 28, 1989-2002.
256. Chen CM, Lin JK, Liu SH, Lin-Shiau SY (2008) Novel regimen through combination of memantine and tea polyphenol for neuroprotection against brain excitotoxicity. J Neurosci Res 86, 2696-2704.
257. Schmitt FA, van Dyck CH, Wichems CH, Olin JT, the Memantine MEM-MD-02 Study Group (2006) Cognitive response to memantine in moderate to severe Alzheimer disease patients already receiving donepezil: An exploratory reanalysis. Alzheimer Dis Assoc Disord 20, 255-262.
258. Schmitt F, Ryan M, Cooper G (2007) A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer's disease. Expert Opin Drug Metab Toxicol 3, 135-141.
259. Rogawski MA, Wenk GL (2003) The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev 9, 275-308.
260. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, Memantine Study, Group (2003) Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 348, 1333-1341.
261. Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nat Rev Drug Discov 5, 160-170.
262. Nakamura T, Lipton SA (2007) S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding. Cell Death Differ 14, 1305-1314.
263. Correia S, Carvalho C, Santos MS, Seiça R, Oliveira CR, Moreira PI (2008) Mechanisms of action of metformin in type 2 diabetes and associated complications: An overview. Mini Rev Med Chem 8, 1343-1354.
264. Imfeld P, Bodmer M, Jick SS, Meier CR (2012) Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: A population-based case-control study. J Am Geriatr Soc 60, 916-921.
265. Chen Y, Zhou K,Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF (2009) Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci U S A 106, 3907-3912.
266. Li Y, Duffy KB, Ottinger MA, Ray B, Bailey JA, Holloway HW, Tweedie D, Perry T, Mattson MP, Kapogiannis D, Sambamurti K, Lahiri DK, Greig NH (2010) GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. J Alzheimers Dis 19, 1205-1219.
267. Ramirez C, Tercero I, Pineda A, Burgos JS (2011) Simvastatin is the statin that most efficiently protects against kainate-induced excitotoxicity and memory impairment. J Alzheimers Dis 24, 161-174.
268. Dolga AM, Nijholt IM, Ostroveanu A, Ten Bosch Q, Luiten PG, Eisel UL (2008) Lovastatin induces neuroprotection through tumor necrosis factor receptor 2 signaling pathways. J Alzheimers Dis 13, 111-122.
269. Tong XK, Lecrux C, Rosa-Neto P, Hamel E (2012) Agedependent rescue by simvastatin of Alzheimer's disease cerebrovascular and memory deficits. J Neurosci 32, 4705-4715.
270. Kimura M, Komatsu H, Ogura H, Sawada K (2005) Comparison of donepezil and memantine for protective effect against amyloid-beta(1-42) toxicity in rat septal neurons. Neurosci Lett 391, 17-21.
271. Akasofu S, Kimura M, Kosasa T, Sawada K, Ogura H (2008) Study of neuroprotection of donepezil, a therapy for Alzheimer's disease. Chem Biol Interact 175, 222-226.
272. Shen H, Kihara T, Hongo H, Wu X, Kem WR, Shimohama S, Akaike A, Niidome T, Sugimoto H (2010) Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of alpha7 nicotinic receptors and internalization of NMDA receptors. Br J Pharmacol 161, 127-139.
273. Fu H, Li W, Liu Y, Lao Y, Liu W, Chen C, Yu H, Lee NT, Chang DC, Li P, Pang Y, Tsim KW, Li M, Han Y (2007) Mitochondrial proteomic analysis and characterization of the intracellular mechanisms of bis(7)-tacrine in protecting against glutamate-induced excitotoxicity in primary cultured neurons. J Proteome Res 6, 2435-2446.
274. Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, Ganguli M (2001) Incidence of Alzheimer's disease in a rural community in India: The Indo-US study. Neurology 57, 985-989.
275. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280, 5892-5901.
276. Kawamoto EM, Scavone C, Mattson MP, Camandola S (2012) Curcumin requires tumor necrosis factor-signaling to alleviate cognitive impairment elicited by lipopolysaccharide. Neurosignals 21, 75-88.
277. Butterfield DA, Perluigi M, Sultana R (2006) Oxidative stress in Alzheimer's disease brain: Newinsights from redox proteomics. Eur J Pharmacol 545, 39-50.
278. Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G, Smith MA (2006) Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65, 631-641.
279. Sun GY, He Y, Chuang DY, Lee JC, Gu Z, Simonyi A, Sun AY (2012) Integrating cytosolic phospholipase A2 with oxidative/nitrosative signaling pathways in neurons: A novel therapeutic strategy for AD. Mol Neurobiol 46, 85-95.
280. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 336, 1216-1222.
281. Simonyi A, Serfozo P, Lehmidi TM, Cui J, Gu Z, Lubahn DB, Sun AY, Sun GY (2012) The neuroprotective effects of apocynin. Front Biosci (Elite Ed) 4, 2183-2193.
282. Grossi C, Francese S, Casini A, Rosi MC, Luccarini I, Fiorentini A, Gabbiani C, Messori L, Moneti G, Casamenti F (2009) Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 17, 423-440.