Signaling pathway cross talk in Alzheimer's disease

Cell Communication and Signaling

Volumn 12, Issue 1, 2014, Pages

  Godoy, Juan A ^a   Rios, Juvenal A ^a   Zolezzi, Juan M ^b   Braidy, Nady ^c   Inestrosa, Nibaldo C ^a,c  

^a PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

^b UNIVERSIDAD DE TARAPACÁ   (Chile)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Alzheimer's disease; Cognitive decline; Neurodegeneration; Neuronal network failure; Reactive oxygen species

Indexed keywords

5' ADENOSINE MONOPHOSPHATE ACTIVATED PROTEIN KINASE; AMYLOID BETA PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN KINASE; SIRTUIN 1; UNCLASSIFIED DRUG; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; TARGET OF RAPAMYCIN KINASE; TRANSCRIPTION FACTOR;

AGING; ALZHEIMER DISEASE; ARTICLE; CELL ACTIVATION; CELL ENERGY; CHOLINERGIC SYSTEM; CLINICAL TRIAL (TOPIC); DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENZYME ACTIVITY; HUMAN; INFLAMMATION; MITOCHONDRIAL DYNAMICS; NERVE CELL; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN AGGREGATION; SIGNAL TRANSDUCTION; SYNAPTIC MEMBRANE; WNT SIGNALING PATHWAY; ANIMAL; METABOLISM; REVIEW;

ALZHEIMER DISEASE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; HUMANS; SIRTUIN 1; TOR SERINE-THREONINE KINASES; TRANSCRIPTION FACTORS; WNT SIGNALING PATHWAY;

EID: 84898426102     PISSN: None     EISSN: 1478811X     Source Type: Journal    
DOI: 10.1186/1478-811X-12-23     Document Type: Article

References (131)

1. Deciphering Alzheimer disease. Selkoe DJ, Mandelkow E, Holtzman D, Cold Spring Harbor Perspect Med 2012 2 011460
2. Mitochondrial abnormalities in Alzheimer's disease. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA, (J Neurosci 2001 21 3017 3023 11312286 (Pubitemid 32323483)
3. Pathways towards and away from Alzheimer's disease. Mattson M, Nature 2004 430 631 639 10.1038/nature02621 15295589 (Pubitemid 39061671)
4. Three decades of Wnts; a personal perspective on how a scientific field developed. Nusse R, Varmus H, EMBO J 2012 31 2670 2682 10.1038/emboj.2012.146 22617420
5. Wnt/β-catenin signaling and disease. Clevers H, Nusse R, Cell 2012 149 1192 1205 10.1016/j.cell.2012.05.012 22682243
6. Proximal events in Wnt signal transduction. Angers S, Moon RT, Nat Rev Mol Cell Biol 2009 10 468 477 19536106
7. WNTs in the vertebrate nervous system nervous system: from patterning to neuronal connectivity. Ciani L, Salinas P, Nat Rev Neurosci 2005 6 351 362 15832199 (Pubitemid 40593481)
8. WNT signaling in neuronal maturation and synaptogenesis. Rosso SB, Inestrosa NC, Frontiers Cell Neurosci 2013 7 103
9. Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Zhang Z, Hartmann H, Do VM, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Sommer B, van de Wetering M, Clevers H, Saftig P, De Strooper B, He X, Yankner BA, Nature 1998 395 698 702 10.1038/27208 9790190 (Pubitemid 28475966)
10. Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by beta-amyloid fibrils. De Ferrari GV, Chacon MA, Barria MI, Garrido JL, Godoy JA, Olivares G, Reyes AE, Alvarez A, Bronfman M, Inestrosa NC, Mol Psychiat 2003 8 195 208 10.1038/sj.mp.4001208 (Pubitemid 36315228)
11. Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons. Alvarez A, Godoy JA, Mullendorff K, Olivares GH, Bronfman M, Inestrosa NC, Exp Cell Res 2004 297 186 196 10.1016/j.yexcr.2004.02.028 15194435 (Pubitemid 38759572)
12. The Wnt pathway, cell-cycle activation and beta-amyloid: novel therapeutic strategies in Alzheimer's disease? Caricasole A, Copani A, Caruso A, Caraci F, Iacovelli L, Sortino MA, Terstappen GC, Nicoletti F, Trends Pharmacol Sci 2003 24 233 238 10.1016/S0165-6147(03)00100-7 12767722 (Pubitemid 36588871)
13. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain. Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, Caruso A, Storto M, Gaviraghi G, Terstappen GC, Nicoletti F, J Neurosci 2004 24 6021 6027 10.1523/JNEUROSCI.1381- 04.2004 15229249 (Pubitemid 38859398)
14. Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease. Rosi MC, Luccarini I, Grossi C, Fiorentini A, Spillantini MG, Prisco A, Scali C, Gianfriddo M, Caricasole A, Terstappen GC, Casamenti F, J Neurochem. 2010 112 1539 1551 10.1111/j.1471-4159.2009.06566.x 20050968
15. Dkk-3 is elevated in CSF and plasma of Alzheimer's disease patients. Zenzmaier C, Marksteiner J, Kiefer A, Berger P, Humpel C, J Neurochem 2009 110 653 661 10.1111/j.1471-4159.2009.06158.x 19457090
16. Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells. Caruso A, Motolese M, Iacovelli L, Caraci F, Copani A, Nicoletti F, Terstappen GC, Gaviraghi G, Caricasole A, J Neurochem 2006 98 364 371 10.1111/j.1471-4159.2006.03867.x 16805831 (Pubitemid 44133142)
17. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. De Ferrari GV, Papassotiropoulos A, Biechele T, Wavrant De-Vrieze F, Avila ME, Major MB, Myers A, Saez K, Henriquez JP, Zhao A, Wollmer MA, Nitsch RM, Hock C, Morris CM, Hardy J, Moon RT, Proceedings of the National Academy of Sciences of the United States of America 2007 104 9434 9439 10.1073/pnas.0603523104 17517621 (Pubitemid 47185797)
18. The secreted Wnt antagonist Dickkopf-1 is required for amyloid-beta-mediated synaptic loss. Purro SA, Dickins EM, Salinas PC, J Neurosci 2012 32 3492 3498 10.1523/JNEUROSCI.4562-11.2012 22399772
19. Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative diseases. Purro SA, Galli S, Salinas PC, J Mol Cell Biol 2014 6 75 80 10.1093/jmcb/mjt049 24449494
20. Clusterin regulates β-amyloid toxicity via Dickkopf-1-driven induction of the Wnt-PCP-JNK pathway. Killick R, Ribe E, Ribe EM, Al-Shawi R, Malik B, Hooper C, Fernandes C, Dobson R, Nolan PM, Lourdusamy A, Furney S, Lin K, Breen G, Wroe R, To AW, Leroy K, Causevic M, Usardi A, Robinson M, Noble W, Williamson R, Lunnon K, Kellie S, Reynolds CH, Bazenet C, Hodges A, Brion JP, Stephenson J, Simons JP, Lovestone S, Molecular psychiatry 2014 19 88 98 19:88-98 10.1038/mp.2012.163 23164821
21. Neuropathological alterations in Alzheimer disease. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT, Cold Spring Harbor Perspect Med 2011 1 006189
22. Wnt-5a occludes Abeta oligomer-induced depression of glutamatergic transmission in hippocampal neurons. Cerpa W, Farias GG, Godoy JA, Fuenzalida M, Bonansco C, Inestrosa NC, Mol Neurodegeneration 2010 5 3 10.1186/1750-1326-5-3
23. Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons. Muñoz FJ, Godoy JA, Cerpa W, Poblete IM, Huidobro-Toro JP, Inestrosa NC, Biochem Biophys Res Commun 2014 444 189 194 10.1016/j.bbrc.2014. 01.031 24440698
24. Wnt-5a modulates recycling of functional GABAA receptors on hippocampal neurons. Coutiño L, Godoy JA, Couve A, Fuenzalida M, Inestrosa NC, J Neurosci 2010 30 8411 8420 10.1523/JNEUROSCI.5736-09.2010 20573888
25. Wnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons. Farias GG, Alfaro IE, Cerpa W, Grabowski CP, Godoy JA, Bonansco C, Inestrosa NC, J Biol Chem 2009 284 15857 15866 10.1074/jbc.M808986200 19332546
26. Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses. Varela-Nallar L, Alfaro IE, Serrano FG, Parodi J, Inestrosa NC, Proc Natl Acad Sci U S A 2010 107 21164 21169 10.1073/pnas.1010011107 21084636
27. Canonical Wnt signaling protects hippocampal neurons from Abeta oligomers: role of non-canonical Wnt-5a/Ca(2+) in mitochondrial dynamics. Silva-Alvarez C, Arrazola MS, Godoy JA, Ordenes D, Inestrosa NC, Frontiers Cell Neurosci 2013 7 97
28. In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model. Vargas J, Fuenzalida M, Inestrosa NC, J Neurosci 2014 34 2191 2202 10.1523/JNEUROSCI.0862-13.2014 24501359
29. Wnt signaling in the nervous system and in Alzheimer's disease. Inestrosa NC, Varela-Nallar L, J Mol Cell Biol 2014 6 64 74 10.1093/jmcb/mjt051 24549157
30. The role of Wnt signaling in neuronal dysfunction in Alzheimer's disease. Inestrosa NC, Toledo EM, Mol Neurodegeneration 2008 3 9 10.1186/1750-1326-3-9
31. Emerging roles of Wnts in the adult nervous system. Inestrosa NC, Arenas E, Nat Rev Neurosci 2010 11 77 86 10.1038/nrn2755 20010950
32. The cholinergic hypothesis of cognitive aging revisited again: cholinergic functional compensation. Dumas JA, Newhouse PA, Pharmacol Biochem Behav 2011 99 254 261 10.1016/j.pbb.2011.02.022 21382398
33. Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme. Inestrosa NC, Alvarez A, Perez CA, Moreno RD, Vicente M, Linker C, Casanueva OI, Soto C, Garrido J, Neuron 1996 16 881 891 10.1016/S0896-6273(00)80108-7 8608006 (Pubitemid 26124065)
34. Neurotoxicity of acetylcholinesterase amyloid beta-peptide aggregates is dependent on the type of Abeta peptide and the AChE concentration present in the complexes. Munoz FJ, Inestrosa NC, FEBS letters 1999 450 205 209 10.1016/S0014-5793(99)00468-8 10359075 (Pubitemid 29219515)
35. The hyperforin derivative IDN5706 occludes spatial memory impairments and neuropathological changes in a double transgenic Alzheimer's mouse model. Cerpa W, Hancke JL, Morazzoni P, Bombardelli E, Riva A, Marin PP, Inestrosa NC, Curr Alzheimer Res 2010 7 126 133 10.2174/156720510790691218 19939230
36. Release of acetylcholinesterase (AChE) from beta-amyloid plaques assemblies improves the spatial memory impairments in APP-transgenic mice. Dinamarca MC, Arrazola M, Toledo E, Cerpa WF, Hancke J, Inestrosa NC, Chem Biol Interact 2008 175 142 149 10.1016/j.cbi.2008.05.026 18599028
37. Tetrahydrohyperforin decreases cholinergic markers associated with amyloid-beta plaques, 4-hydroxynonenal formation, and caspase-3 activation in AbetaPP/PS1 mice. Carvajal FJ, Zolezzi JM, Tapia-Rojas C, Godoy JA, Inestrosa NC, J Alzheimers Dis 2013 36 99 118 23568104
38. Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system. Jensen M, Hoerndli FJ, Brockie PJ, Wang R, Johnson E, Maxfield D, Francis MM, Madsen DM, Maricq AV, Cell 2012 149 173 187 10.1016/j.cell.2011.12.038 22464329
39. Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system. Jensen M, Brockie PJ, Maricq AV, Cell Cycle 2012 11 2585 2586 10.4161/cc.21138 22781061
40. Antioxidant approaches for the treatment of Alzheimer's disease. Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, Lee HG, Perry G, Expert Rev Neurother 2010 10 1201 1208 10.1586/ern.10.74 20586698
41. Inhibitors of catalase-amyloid interactions protect cells from beta-amyloid-induced oxidative stress and toxicity. Habib LK, Lee MT, Yang J, J Biol Chem 2010 285 38933 38943 10.1074/jbc.M110.132860 20923778
42. Trolox and 17beta-estradiol protect against amyloid beta-peptide neurotoxicity by a mechanism that involves modulation of the Wnt signaling pathway. Quintanilla RA, Munoz FJ, Metcalfe MJ, Hitschfeld M, Olivares G, Godoy JA, Inestrosa NC, J Biol Chem 2005 280 11615 11625 10.1074/jbc.M411936200 15659394 (Pubitemid 40418475)
43. Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer's disease. Inestrosa NC, Carvajal FJ, Zolezzi JM, Tapia-Rojas C, Serrano F, Karmelic D, Toledo EM, Toro A, Toro J, Santos MJ, J Alzheimers Dis 2013 33 941 959 23109558
44. Increased expression of Wnt-1 in schizophrenic brains. Miyaoka T, Seno H, Ishino H, Schizophr Res 1999 38 1 6 10.1016/S0920-9964(98)00179-0 10427605 (Pubitemid 29333595)
45. Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated phosphorylation of tau in transfected mammalian cells. Wagner U, Brownlees J, Irving NG, Lucas FR, Salinas PC, Miller CC, Febs Lett 1997 411 369 372 10.1016/S0014-5793(97)00733-3 9271238 (Pubitemid 27301487)
46. AMP-activated protein kinase: new regulation, new roles? Carling D, Thornton C, Woods A, Sanders MJ, Biochem J 2012 445 11 27 10.1042/BJ20120546 22702974
47. Identification of nitric oxide as an endogenous activator of the AMP-activated protein kinase in vascular endothelial cells. Zhang J, Xie Z, Dong Y, Wang S, Liu C, Zou MH, J Biol Chem 2008 283 27452 27461 10.1074/jbc. M802578200 18693249
48. AMPK, insulin resistance, and the metabolic syndrome. Ruderman NB, Carling D, Prentki M, Cacicedo JM, J Clin Invest 2013 123 2764 2772 10.1172/JCI67227 23863634
49. AMP-activated protein kinase: a target for drugs both ancient and modern. Hardie DG, Ross FA, Hawley SA, Chem Biol 2012 19 1222 1236 10.1016/j.chembiol. 2012.08.019 23102217
50. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1 Jager S, Handschin C, St-Pierre J, Spiegelman BM, Proc Natl Acad Sci U S A 2007 104 12017 12022 10.1073/pnas.0705070104 17609368 (Pubitemid 47185622)
51. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. Greer EL, Oskoui PR, Banko MR, Maniar JM, Gygi MP, Gygi SP, Brunet A, J Biol Chem 2007 282 30107 30119 10.1074/jbc.M705325200 17711846 (Pubitemid 350035296)
52. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ, Science 2011 331 456 461 10.1126/science.1196371 21205641
53. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Alers S, Loffler AS, Wesselborg S, Stork B, Mol Cell Biol 2012 32 2 11 10.1128/MCB.06159-11 22025673
54. TOR on the brain. Garelick MG, Kennedy BK, Exp Gerontol 2011 46 155 163 10.1016/j.exger.2010.08.030 20849946
55. The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis. Caberlotto L, Lauria M, Nguyen TP, Scotti M, PloS One 2013 8 78919 10.1371/journal.pone.0078919 24265728
56. Dysfunction of the mTOR pathway is a risk factor for Alzheimer's disease. Yates SC, Zafar A, Hubbard P, Nagy S, Durant S, Bicknell R, Wilcock G, Christie S, Esiri MM, Smith AD, Nagy Z, Acta Neuropathologica Commun 2013 1 3 10.1186/2051-5960-1-3
57. Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells. Greco SJ, Sarkar S, Johnston JM, Tezapsidis N, Biochem Biophys Res Commun 2009 380 98 104 10.1016/j.bbrc.2009.01.041 19166821
58. AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid beta-peptide exposure. Thornton C, Bright NJ, Sastre M, Muckett PJ, Carling D, Biochem Med 2011 434 503 512
59. AMPK is abnormally activated in tangle- and pre-tangle-bearing neurons in Alzheimer's disease and other tauopathies. Vingtdeux V, Davies P, Dickson DW, Marambaud P, Acta Neuropathol 2011 121 337 349 10.1007/s00401-010-0759-x 20957377
60. AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. Vingtdeux V, Giliberto L, Zhao H, Chandakkar P, Wu Q, Simon JE, Janle EM, Lobo J, Ferruzzi MG, Davies P, Marambaud P, J Biol Chem 2010 285 9100 9113 10.1074/jbc.M109.060061 20080969
61. Roles of AMP-activated protein kinase in Alzheimer's disease. Cai Z, Yan LJ, Li K, Quazi SH, Zhao B, Neuromolecular Med 2012 14 1 14 10.1007/s12017-012- 8173-2 22367557
62. Down-regulation of amyloid-beta through AMPK activation by inhibitors of GSK-3beta in SH-SY5Y and SH-SY5Y-AbetaPP695 cells. Cai Z, Li B, Li K, Zhao B, J Alzheimers Dis 2012 29 89 98 22214783
63. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Los MJ, Progr Neurobiol 2014 112 24 49
64. Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Tan CC, Yu JT, Tan MS, Jiang T, Zhu XC, Tan L, Neurobiol Aging 2013 35 941 957 24360503
65. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. 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, Proceedings of the National Academy of Sciences of the United States of America 2009 106 3907 3912 10.1073/pnas.0807991106 19237574
66. Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models. Anekonda TS, Wadsworth TL, Sabin R, Frahler K, Harris C, Petriko B, Ralle M, Woltjer R, Quinn JF, J Alzheimers Dis 2011 23 21 35 20930278
67. Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both beta-amyloid production and clearance. Zhu Z, Yan J, Jiang W, Yao XG, Chen J, Chen L, Li C, Hu L, Jiang H, Shen X, J Neurosci 2013 33 13138 13149 10.1523/JNEUROSCI.4790-12.2013 23926267
68. Apigenin attenuates copper-mediated beta-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model. Zhao L, Wang JL, Wang YR, Fa XZ, Brain Res 2013 1492 33 45 23178511
69. Curcumin-induced upregulation of the anti-tau cochaperone BAG2 in primary rat cortical neurons. Patil SP, Tran N, Geekiyanage H, Liu L, Chan C, Neurosci Lett 2013 554 121 125 24035895
70. Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Congdon EE, Wu JW, Myeku N, Figueroa YH, Herman M, Marinec PS, Gestwicki JE, Dickey CA, Yu WH, Duff KE, Autophagy 2012 8 609 622 10.4161/auto.19048 22361619
71. Methylene blue induces macroautophagy through 5' adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation. Xie L, Li W, Winters A, Yuan F, Jin K, Yang S, Front Cell Neurosci 2013 7 56 23653592
72. A butyrolactone derivative 3BDO alleviates memory deficits and reduces amyloid-beta deposition in an AbetaPP/PS1 transgenic mouse model. Wei L, Yang H, Xie Z, Yang S, Yang H, Zhao C, Wang P, Xu S, Miao J, Zhao B, Bi J, J Alzheimers Dis 2012 30 531 543 22451314
73. Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APPswe/PS1dE9 Transgenic Mice. Shi JQ, Wang BR, Tian YY, Xu J, Gao L, Zhao SL, Jiang T, Xie HG, Zhang YD, CNS Neurosci Ther 2013 19 871 881 10.1111/cns.12144 23889921
74. Autophagy enhancer carbamazepine alleviates memory deficits and cerebral amyloid-beta pathology in a mouse model of Alzheimer's disease. Li L, Zhang S, Zhang X, Li T, Tang Y, Liu H, Yang W, Le W, Curr Alzheimer Res 2013 10 433 441 10.2174/1567205011310040008 23305067
75. Latrepirdine (Dimebon(R)), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Steele JW, Gandy S, Autophagy 2013 9 617 618 10.4161/auto.23487 23380933
76. Effects of rapamycin and TOR on aging and memory: implications for Alzheimer's disease. Santos RX, Correia SC, Cardoso S, Carvalho C, Santos MS, Moreira PI, J Neurochem 2011 117 927 936 10.1111/j.1471-4159.2011.07262.x 21447003
77. Mammalian target of rapamycin: a valid therapeutic target through the autophagy pathway for Alzheimer's disease? Cai Z, Zhao B, Li K, Zhang L, Li C, Quazi SH, Tan Y, J Neurosci Res 2012 90 1105 1118 10.1002/jnr.23011 22344941
78. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. Caccamo A, Majumder S, Richardson A, Strong R, Oddo S, J Biol Chem 2010 285 13107 13120 10.1074/jbc.M110.100420 20178983
79. Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. Majumder S, Richardson A, Strong R, Oddo S, PLoS One 2011 6 25416 10.1371/journal.pone.0025416 21980451
80. Role of Sirt1 during the ageing process: relevance to protection of synapses in the brain. Godoy JA, Zolezzi JM, Braidy N, Inestrosa NC, Mol Neurobiol 2013 doi:10.1007/s12035-014-8645-5
81. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Rose G, Dato S, Altomare K, Bellizzi D, Garasto S, Greco V, Passarino G, Feraco E, Mari V, Barbi C, BonaFe M, Franceschi C, Tan Q, Boikos S, Yashin AI, De Benedictis G, Exp Gerontol 2003 38 1065 1070 10.1016/S0531-5565(03)00209-2 14580859 (Pubitemid 37324417)
82. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B, Mol Cell Biol 2007 27 8807 8814 10.1128/MCB.01636-07 17923681
83. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C, J Mol Biol 2008 382 790 801 10.1016/j.jmb.2008.07.048 18680753
84. Regulation of PGC-1, a nodal regulator of mitochondrial biogenesis. Fernandez-Marcos PJ, Auwerx J, Am J Clin Nutr 2011 93 884S 890 10.3945/ajcn.110.001917 21289221
85. SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1 Nemoto S, Fergusson MM, Finkel T, J Biol Chem 2005 280 16456 16460 10.1074/jbc.M501485200 15716268 (Pubitemid 40616776)
86. PPARgamma co-activator-1alpha (PGC-1alpha) reduces amyloid-beta generation through a PPARgamma-dependent mechanism. Katsouri L, Parr C, Bogdanovic N, Willem M, Sastre M, J Alzheimers Dis 2011 25 151 162 21358044
87. PGC-1 and PGC-1β regulate mitochondrial density in neurons. Wareski P, Vaarmann A, Choubey V, Safiulina D, Liiv J, Kuum M, Kaasik A, J Biol Chem 2009 284 21379 21385 10.1074/jbc.M109.018911 19542216
88. SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes. Yamamoto T, Shimano H, Nakagawa Y, Ide T, Yahagi N, Matsuzaka T, Nakakuki M, Takahashi A, Suzuki H, Sone H, Toyoshima H, Sato R, Yamada N, J Biol Chem 2004 279 12027 12035 14722127 (Pubitemid 38445764)
89. Mitochondrial metabolism, sirtuins, and aging. Sack MN, Finkel T, Cold Spring Harb Perspect Biol 2012 4 doi:10.1101/cshperspect.a013102.
90. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA, Cell Metabol 2012 15 675 690 10.1016/j.cmet.2012.04.003
91. Metabolic stress modulates Alzheimer's beta-secretase gene transcription via SIRT1-PPARgamma-PGC-1 in neurons. Wang R, Li JJ, Diao S, Kwak YD, Liu L, Zhi L, Bueler H, Bhat NR, Williams RW, Park EA, Liao FF, Cell Metab 2013 17 685 694 10.1016/j.cmet.2013.03.016 23663737
92. Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. Hardy J, J Alzheimers Dis 2006 9 151 153 16914853 (Pubitemid 44253307)
93. Has the amyloid cascade hypothesis for Alzheimer's disease been proved? Hardy J, Curr Alzheimer Res 2006 3 71 73 10.2174/156720506775697098 16472206
94. Alzheimer's disease: the amyloid cascade hypothesis. Hardy JA, Higgins GA, Science 1992 256 184 185 10.1126/science.1566067 1566067
95. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J, Nature 1991 349 704 706 10.1038/349704a0 1671712 (Pubitemid 21912142)
96. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi P, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH, Nature 1995 375 754 760 10.1038/375754a0 7596406
97. Pathogenesis of Alzheimer's disease. Swerdlow RH, Clin Interv Aging 2007 2 347 359 18044185
98. The Alzheimer's disease mitochondrial cascade hypothesis: progress and perspectives. Swerdlow RH, Burns JM, Khan SM, Biochim Biophys Acta 2013 S0925-4439 00289 5
99. A «mitochondrial cascade hypothesis» for sporadic Alzheimer's disease. Swerdlow RH, Khan SM, Med Hypotheses 2004 63 8 20 10.1016/j.mehy.2003. 12.045 15193340 (Pubitemid 38887104)
100. Mitochondria and Alzheimer's disease. Piaceri I, Rinnoci V, Bagnoli S, Failli Y, Sorbi S, J Neurol Sci 2012 322 31 34 10.1016/j.jns.2012.05.033 22694975
101. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Sorbi S, Bird ED, Blass JP, Ann Neurol 1983 13 72 78 10.1002/ana.410130116 6219611 (Pubitemid 13224203)
102. Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease. Chandrasekaran K, Giordano T, Brady DR, Stoll J, Martin LJ, Rapoport SI, Brain Res Mol Brain Res 1994 24 336 340 10.1016/0169-328X(94)90147- 3 7968373 (Pubitemid 24202871)
103. The calpains in aging and aging-related diseases. Nixon RA, Ageing Res Rev 2003 2 407 418 10.1016/S1568-1637(03)00029-1 14522243 (Pubitemid 37159401)
104. Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells. Kruman I, Guo Q, Mattson MP, J Neurosci Res 1998 51 293 308 10.1002/(SICI)1097-4547(19980201)51:3<293: :AID-JNR3>3.0.CO;2-B 9486765 (Pubitemid 28078461)
105. Mitochondrial fragmentation in neurodegeneration. Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E, Nat Rev Neurosci 2008 9 505 518 10.1038/nrn2417 18568013 (Pubitemid 351873464)
106. Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease. Gu XM, Huang HC, Jiang ZF, Neurosci Bull 2012 28 631 640 10.1007/s12264-012-1270-2 22968595
107. PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling. Jones AW, Yao Z, Vicencio JM, Karkucinska-Wieckowska A, Szabadkai G, Mitochondrion 2012 12 86 99 10.1016/j.mito.2011.09.009 21983689
108. Sustained expression of PGC-1alpha in the rat nigrostriatal system selectively impairs dopaminergic function. Ciron C, Lengacher S, Dusonchet J, Aebischer P, Schneider BL, Hum Mol Genet 2012 21 1861 1876 10.1093/hmg/ddr618 22246294
109. Deconstructing mitochondrial dysfunction in Alzheimer disease. Garcia-Escudero V, Martin-Maestro P, Perry G, Avila J, Oxid Med Cell Longev 2013 2013 162152 23840916
110. Mitochondrial abnormalities in Alzheimer's disease: possible targets for therapeutic intervention. Silva DF, Selfridge JE, Lu J, EL, Cardoso SM, Swerdlow RH, Adv Pharmacol 2012 64 83 126 22840745
111. Dietary zeolite supplementation reduces oxidative damage and plaque generation in the brain of an Alzheimer's disease mouse model. Montinaro M, Uberti D, Maccarinelli G, Bonini SA, Ferrari-Toninelli G, Memo M, Life Sci 2013 92 903 910 10.1016/j.lfs.2013.03.008 23562853
112. Dietary supplementation with Salvia sahendica attenuates acetylcholinesterase activity and increases mitochondrial transcription factor A and antioxidant proteins in the hippocampus of amyloid beta-injected rats. Foolad F, Khodagholi F, J Pharm Pharmacol 2013 65 1555 1562 10.1111/jphp.12116 24028623
113. Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer's mice and cells. Dragicevic N, Delic V, Cao C, Copes N, Lin X, Mamcarz M, Wang L, Arendash GW, Bradshaw PC, Neuropharmacology 2012 63 1368 1379 10.1016/j.neuropharm.2012.08.018 22959965
114. Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. Navarro A, Gomez C, Lopez-Cepero JM, Boveris A, Am J Physiol Regul Integr Comp Physiol 2004 286 505 511 10.1152/ajpregu.00208.2003 14615275
115. Exercise training increases mitochondrial biogenesis in the brain. Steiner JL, Murphy EA, McClellan JL, Carmichael MD, Davis JM, J Appl Physiol 2011 111 1066 1071 10.1152/japplphysiol.00343.2011 21817111
116. Physical exercise as a possible strategy for brain protection: evidence from mitochondrial-mediated mechanisms. Marques-Aleixo I, Oliveira PJ, Moreira PI, Magalhaes J, Ascensao A, Prog Neurobiol 2012 99 149 162 10.1016/j.pneurobio. 2012.08.002 22940590
117. Mitochondrial membrane permeabilisation by amyloid aggregates and protection by polyphenols. Camilleri A, Zarb C, Caruana M, Ostermeier U, Ghio S, Hogen T, Schmidt F, Giese A, Vassallo N, Biochim Biophys Acta 1828 2013 2532 2543
118. Age-associated changes in oxidative stress and NAD + metabolism in human tissue. Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ, Plos One 2012 7 42357 10.1371/journal.pone.0042357 22848760
119. NAD + metabolism and oxidative stress: the golden nucleotide on a crown of thorns. Massudi H, Grant R, Guillemin GJ, Braidy N, Redox Rep 2012 17 28 46 10.1179/1351000212Y.0000000001 22340513
120. Pathophysiological relevance of mitochondria in NAD + metabolism. di Lisa F, Ziegler M, FEBS Lett 2001 492 4 8 10.1016/S0014-5793(01)02198-6 11248227 (Pubitemid 32206710)
121. Apoptosis inducing factor and PARP mediated injury in the MPTP mouse model of Parkinson's disease. Wang H, Schimoji M, Yu SW, Dawson TM, Dawson VL, Ann N Y Acad Sci 2003 991 132 139 12846982 (Pubitemid 36793809)
122. Enzymes in poly(ADP-Ribose) Metabolism. Meyer R, Meyer-Ficca M, Jacobsen E, Jacobsen M, Poly(ADP-Ribosyl)ation New York: Springer-Landes Bioscience, Burkle A, 2006
123. Poly(ADP-ribose) polymerase-1 mediated cell death in astrocytes required NAD + depletion and mitochondrial permeability transition. Alano CC, Ying W, Swanson RA, J Biol Chem 2004 279 18895 18902 10.1074/jbc.M313329200 14960594 (Pubitemid 38623317)
124. Mapping NAD (+) metabolism in the brain of ageing Wistar rats: potential targets for influencing brain senescence. Braidy N, Poljak A, Grant R, Jayasena T, Mansour H, Chan-Ling T, Guillemin GJ, Smythe G, Sachdev P, Biogerontology 2013 15 177 98 24337988
125. Ryan L, Update on Alzheimer's disease clinical trials. National Institutes on Aging (NIA), National Institutes on Health (NIH), on National Alzheimer's Coordinating Center (NACC), revised February 17th, 2014 https://www.alz.washington.edu/NONMEMBER/SPR12/Ryan.pdf
126. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S, Am J Geriatr Psychiatry 2005 13 950 958 16286438 (Pubitemid 46638661)
127. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, Zvartau-Hind ME, Hosford DA, Roses AD, Pharmacogenom J 2006 6 246 254 (Pubitemid 44137951)
128. Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O'Banion K, Klockgether T, Van Leuven F, Landreth GE, Brain 2005 128 1442 1453 10.1093/brain/awh452 15817521 (Pubitemid 40826196)
129. The role of peroxisome proliferator-activated receptor-gamma (PPARγ) in Alzheimer's disease: therapeutic implications. Jiang Q, Heneka M, Landreth GE, CNS Drugs 2008 22 1 14 10.2165/00023210-200822010-00001 18072811 (Pubitemid 350243363)
130. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE, J Am Assoc Med 2007 298 1180 1188 10.1001/jama.298.10. 1180 (Pubitemid 47403104)
131. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Geldmacher DS, Fritsch T, McClendon MJ, Landreth G, Arch Neurol 2011 68 45 50 20837824 Tecnológico