Abstract
Autophagy is an essential degradation pathway in clearing abnormal protein aggregates in mammalian cells and is responsible for protein homeostasis and neuronal health. Several studies have shown that autophagy deficits occurred in early stage of Alzheimer’s disease (AD). Autophagy plays an important role in generation and metabolism of β-amyloid (Aβ), assembling of tau and thus its malfunction may lead to the progress of AD. By considering the above evidences, autophagy may be a new target in developing drugs for AD. So far, a number of mammalian target of rapamycin (mTOR)-dependent and independent autophagy modulators have been identified to have positive effects in AD treatment. In this review, we summarized the latest progress supporting the role for autophagy deficits in AD and the potential therapeutic effects of autophagy modulators in AD.
Similar content being viewed by others
References
Agarraberes FA, Terlecky SR, Dice JF (1997) An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol 137(4):825–834
An WL, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, Iqbal IG, Winblad B, Pei JJ (2003) Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer’s disease. Am J Pathol 163(2):591–607
Anekonda TS, Quinn JF (2011) Calcium channel blocking as a therapeutic strategy for Alzheimer’s disease: the case for isradipine. Biochim Biophys Acta 1812(12):1584–1590
Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL (2014) Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol 206(5):655–670
Avrahami L, Farfara D, Shaham Kol M, Vassar R, Frenkel D, Eldar-Finkelman H (2013) Inhibition of glycogen synthase kinase-3 ameliorates β-amyloid pathology and restores lysosomal acidification and mammalian target of rapamycin activity in the Alzheimer disease mouse model: in vivo and in vitro studies. J Biol Chem 288:1295–1306
Belinson H, Lev D, Masliah E, Michaelson DM (2008) Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits. J Neurosci 28(18):4690–4701
Bell KF, Claudio CA (2006) Altered synaptic function in Alzheimer’s disease. Eur J Pharmacol 545(1):11–21
Bernard A, Klionsky DJ (2014) Defining the membrane precursor supporting the nucleation of the phagophore. Autophagy 10(1):1–2
Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 28(27):6926–6937
Caccamo A, De Pinto V, Messina A, Branca C, Oddo S (2014) Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer’s disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature. J Neurosci 34(23):7988–7998
Cavieres VA, González A, Muñoz VC, Yefi CP, Bustamante HA, Barraza RR, Tapia-Rojas C, Otth C, Barrera MJ, González C, Mardones GA, Inestrosa NC, Burgos PV (2015) Tetrahydrohyperforin inhibits the proteolytic processing of amyloid precursor protein and enhances its degradation by Atg5-dependent autophagy. PLoS ONE 10(8):e0136313
Chiang HL, Terlecky SR, Plant CP, Dice JF (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246(4928):382–385
Cho MH, Cho K, Kang HJ, Jeon EY, Kim HS, Kwon HJ, Kim HM, Kim DH, Yoon SY (2014) Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy 10(10):1761–1775
Cho SJ, Yun SM, Jo C, Lee DH, Choi KJ, Song JC, Park SI, Kim YJ, Koh YH (2015) SUMO1 promotes Aβ production via the modulation of autophagy. Autophagy 11(1):100–112
Congdon EE, Wu JW, Myeku N, Figueroa YH, Herman M, Marinec PS, Gestwicki JE, Dickey CA, Yu WH (2012) Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy 8(4):609–622
Correia SC, Resende R, Moreira PI (2015) Pereira CM (2015) Alzheimer’s disease-related misfolded proteins and dysfunctional organelles on autophagy menu. DNA Cell Biol 34(4):261–273
Cuervo AM (2010) Chaperone-mediated autophagy: selectivity pays off. Trends Endocrinol Metab 21(3):142–150
Cuervo AM, Dice JF (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273:501–503
Cuervo AM, Dice JF, Knecht E (1997) A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J Biol Chem 272(9):5606–5615
Das U, Scott DA, Ganguly A, Koo EH, Tang Y, Roy S (2013) Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. Neuron 79(3):447–460
Dice J (2007) Chaperone-mediated autophagy. Autophagy 3:295–299
Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L et al (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11:1305–1314
Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T (2008) The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 19(5):2092–2100
Hamano T, Gendron TF, Causevic E, Yen SH, Lin WL, Isidoro C, Deture M, Ko LW (2008) Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression. Eur J Neurosci 27(5):1119–1130
Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A, Basun H (2009) Lithium trial in Alzheimer’s disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry 70(6):922–923
Hayashi S, Sato N, Yamamoto A, Ikegame Y, Nakashima S, Ogihara T, Morishita R (2009) Alzheimer disease-associated peptide, amyloid β40, inhibits vascular regeneration with induction of endothelial autophagy. Arterioscler Thromb Vasc Biol 29(11):1909–1915
Ingelsson M, Fukumoto H, Newell KL, Growdon JH, Hedley-Whyte ET, Frosch MP, Albert MS, Hyman BT, Irizarry MC (2004) Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology 62(6):925–931
Inoue K, Rispoli J, Kaphzan H, Klann E, Chen EI, Kim J, Komatsu M, Abeliovich A (2012) Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway. Mol Neurodegener 7:48
Jewell JL, Russell RC, Guan KL (2013) Amino acid signalling upstream of mTOR. Nat Rev Mol Cell Biol 14(3):133–139
Ji ZS, Müllendorff K, Cheng IH, Miranda RD, Huang Y, Mahley RW (2006) Reactivity of apolipoprotein E4 and amyloid beta peptide: lysosomal stability and neurodegeneration. J Biol Chem 281(5):2683–2692
Jiang T, Yu JT, Zhu XC, Tan MS, Wang HF, Cao L, Zhang QQ, Shi JQ, Gao L, Qin H, Zhang YD, Tan L (2014a) Temsirolimus promotes autophagic clearance of amyloid-β and provides protective effects in cellular and animal models of Alzheimer’s disease. Pharmacol Res 81:54–63
Jiang T, Yu JT, Zhu XC, Zhang QQ, Cao L, Wang HF, Tan MS, Gao Q, Qin H, Zhang YD, Tan L (2014b) Temsirolimus attenuates tauopathy in vitro and in vivo by targeting tau hyperphosphorylation and autophagic clearance. Neuropharmacology 85:121–130
Jo C, Gundemir S, Pritchard S, Jin YN, Rahman I, Johnson GV (2014) Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nat Commun 5:3496
Kaushik S, Cuervo AM (2012) Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol 22(8):407–417
Kessing LV, Forman JL, Andersen PK (2010) Does lithium protect against dementia? Bipolar Disord 12(1):87–94
Kim YM, Jung CH, Seo M, Kim EK, Park JM, Bae SS, Kim DH (2015) mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. Mol Cell 57(2):207–218
Koga H, Cuervo AM (2011) Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. Neurobiol Dis 43(1):29–37
Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N (2004) The role of autophagy during the early neonatal starvation period. Nature 432(7020):1032–1036
Lai AY, McLaurin J (2012) Inhibition of amyloid-beta peptide aggregation rescues the autophagic deficits in the TgCRND8 mouse model of Alzheimer disease. Biochim Biophys Acta 1822(10):1629–1637
Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146–1158
Lee KM, Hwang SK, Lee JA (2013) Neuronal autophagy and neurodevelopmental disorders. Exp Neurobiol 22(3):133–142
Lee JK, Jin HK, Park MH, Kim BR, Lee PH, Nakauchi H, Carter JE, He X, Schuchman EH, Bae JS (2014) Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer’s disease. J Exp Med 211(8):1551–1570
Lee HR, Shin HK, Park SY, Kim HY, Bae SS, Lee WS, Rhim BY, Hong KW, Kim CD (2015) Cilostazol upregulates autophagy via SIRT1 activation: reducing amyloid-β peptide and APP-CTFβ levels in neuronal cells. PLoS ONE 10(8):e0134486
Li M, Sun M, Liu Y, Yu J, Yang H, Fan D, Chui D (2010) Copper downregulates neprilysin activity through modulation of neprilysin degradation. J Alzheimer’s Dis 19(1):161–169
Li L, Zhang S, Zhang X, Li T, Tang Y, Liu H, Yang W, Le W (2013) Autophagy enhancer carbamazepine alleviates memory deficits and cerebral amyloid-β pathology in a mouse model of Alzheimer’s disease. Curr Alzheimer Res 10:433–441
Lim F, Hernández F, Lucas JJ, Gómez-Ramos P, Morán MA, Avila J (2001) FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and tau filaments in forebrain. Mol Cell Neurosci 18(6):702–714
Lin WL, Lewis J, Yen SH, Hutton M, Dickson DW (2003) Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tau. J Neurocytol 32(9):1091–1105
Ling D, Magallanes M, Salvaterra PM (2014) Accumulation of amyloid-like Aβ1-42 in AEL (autophagy–endosomal–lysosomal) vesicles: potential implications for plaque biogenesis. ASN Neuro 6(2):95–109
Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan J (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci USA 107(32):14164–14169
Liu C, Gao Y, Barrett J, Hu B (2010) Autophagy and protein aggregation after brain ischemia. J Neurochem 115(1):68–78
Macdonald A, Briggs K, Poppe M, Higgins A, Velayudhan L, Lovestone S (2008) A feasibility and tolerability study of lithium in Alzheimer’s disease. Int J Geriatr Psychiatry 23(7):704–711
Maday S, Holzbaur EL (2014) Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway. Dev Cell 30(1):71–85
Maday S, Wallace KE, Holzbaur EL (2012) Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J Cell Biol 196:407–417
Majumder S, Richardson A, Strong R, Oddo S (2011) Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. PLoS ONE 6(9):e25416
Mariño G, Madeo F, Kroemer G (2011) Autophagy for tissue homeostasis and neuroprotection. Curr Opin Cell Biol 23(2):198–206
Mazure NM, Pouysségur J (2010) Hypoxia-induced autophagy: Cell death or cell survival? Curr Opin Cell Biol 22(2):177–180
Miners JS, Baig S, Palmer J, Palmer LE, Kehoe PG, Love S (2008) Abeta-degrading enzymes in Alzheimer’s disease. Brain Pathol 18(2):240–252
Mizushima N (2005) A(beta) generation in autophagic vacuoles. J Cell Biol 171(1):15–17
Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15(3):1101–1111
Monastyrska I, Rieter E, Klionsky DJ, Reggiori F (2009) Multiple roles of the cytoskeleton in autophagy. Biol Rev Camb Philos Soc 84(3):431–448
Moreau K, Fleming A, Imarisio S, Lopez Ramirez A, Mercer JL, Jimenez-Sanchez M, Bento CF, Puri C, Zavodszky E, Siddiqi F, Lavau CP, Betton M, O’Kane CJ, Wechsler DS, Rubinsztein DC (2014) PICALM modulates autophagy activity and tau accumulation. Nat Commun 5:4998
Nalivaeva NN, Belyaev ND, Turner AJ (2009) Sodium valproate: an old drug with new roles. Trends Pharmacol Sci 30(10):509–514
Nilsson P, Saido TC (2014) Dual roles for autophagy: degradation and secretion of Alzheimer’s disease Aβ peptide. BioEssays 36(6):570–578
Nilsson P, Sekiguchi M, Akagi T, Izumi S, Komori T, Hui K, Sörgjerd K, Tanaka M, Saito T, Iwata N, Saido TC (2015) Autophagy-related protein 7 deficiency in amyloid β (Aβ) precursor protein transgenic mice decreases Aβ in the multivesicular bodies and induces Aβ accumulation in the Golgi. Am J Pathol 185:305–313
Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, CataldoA Cuervo AM (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. JNeuropathol Exp Neurol 64:113–122
Nunes PV, Forlenza OV, Gattaz WF (2007) Lithium and risk for Alzheimer’s disease in elderly patients with bipolar disorder. Br J Psychiatry 190:359–360
Omata Y, Lim YM, Akao Y, Tsuda L (2014) Age-induced reduction of autophagy-related gene expression is associated with onset of Alzheimer’s disease. Am J Neurodegener Dis 3(3):134–142
Papp D, Kovács T, Billes V, Varga M, Tarnóci A, Hackler L Jr, Puskás LG, Liliom H, Tárnok K, Schlett K, Borsy A, Pádár Z, Kovács AL, Hegedűs K, Juhász G, Komlós M, Erdős A, Gulyás B, Vellai T (2015) AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects. Autophagy 27:0
Park JS, Kim DH, Yoon SY (2016) Regulation of amyloid precursor protein processing by its KFERQ motif. BMB Rep (Epub ahead of print)
Pei JJ, Hugon J (2008) mTOR-dependent signalling in Alzheimer’s disease. J Cell Mol Med 12(6B):2525–2532
Peric A, Annaert W (2015) Early etiology of Alzheimer’s disease: Tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathol 129(3):363–381
Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Invest 118(6):2190–2199
Rodríguez-Martín T, Cuchillo-Ibáñez Noble W, Nyenya F, Anderton BH, Hanger DP (2013) Tau phosphorylation affects its axonal transport and degradation. Neurobiol Aging 34(9):2146–2157
Rubinsztein DC, DiFiglia M, Heintz N, Nixon RA, Qin ZH, Ravikumar B, Stefanis L, Tolkovsky A (2005) Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy 1(1):11–22
Rubinsztein DC, Mariño G, Kroemer G (2011) Autophagy and aging. Cell 146(5):682–695
Russell RC, Tian Y, Yuan H, Park HW, Chang YY, Kim J, Kim H, Neufeld TP, Dillin A, Guan KL (2013) ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol 15(7):741–750
Sanchez-Varo R, Trujillo-Estrada L, Sanchez-Mejias E, Torres M, Baglietto-Vargas D, Moreno-Gonzalez I, De Castro V, Jimenez S, Ruano D, Vizuete M, Davila JC, Garcia-Verdugo JM, Jimenez AJ, Vitorica J, Gutierrez A (2012) Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus. Acta Neuropathol 123(1):53–70
Sarkar S, Rubinsztein DC (2008) Huntington’s disease: degradation of mutant huntingtin by autophagy. FEBS J 275(17):4263–4270
Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC (2007a) Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem 282(8):5641–5652
Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL, Webster JA, Lewis TA, O’Kane CJ, Schreiber SL, Rubinsztein DC (2007b) Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol 3(6):331–338
Sarkar S, Ravikumar B, Floto RA, Rubinsztein DC (2009) Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ 16(1):46–56
Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26(7):1749–1760
Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J (2006) Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem 281(20):14474–14485
Son SM, Jung ES, Shin HJ, Byun J, Mook-Jung I (2012) Aβ-induced formation of autophagosomes is mediated by RAGE-CaMKKβ-AMPK signaling. Neurobiol Aging 33(5):1006.e11–1006.e23
Song Z, Zhao D, Yang L (2013) Molecular mechanisms of neurodegeneration mediated by dysfunctional subcellular organelles in transmissible spongiform encephalopathies. Acta Biochim Biophys Sin (Shanghai) 45(6):452–464
Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, Richardson A, Strong R, Galvan V (2010) Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer’s disease. PLoS ONE 5(4):e9979
Su JH, Cummings BJ, Cotman CW (1993) Identification and distribution of axonal dystrophic neuritis in Alzheimer’s disease. Brain Res 625(2):228–237
Sun M, Zhou T, Zhou L, Chen Q, Yu Y, Yang H, Zhong K, Zhang X, Xu F, Cai S, Yu A, Zhang H, Xiao R, Xiao D, Chui D (2012) Formononetin protects neurons against hypoxia-induced cytotoxicity through upregulation of ADAM10 and sAβPPα. J Alzheimer’s Dis 28(4):795–808
Suzuki K, Terry RD (1967) Fine structural localization of acid phosphatase in senile plaques in Alzheimer’s presenile dementia. Acta Neuropathol 8:276–284
Sweetlove M (2012) Phase III CONCERT trial of latrepirdine. Negative results. Pharm Med 26(2):113–115
Tang YP (2003) Genetic studies in Alzheimer’s disease. Dialog Clin Neurosci 5(1):17–26
Tian Y, Chang JC, Greengard P, Flajolet M (2014) The convergence of endosomal and autophagosomal pathways: implications for APP-CTF degradation. Autophagy 10(4):694–696
Wang Y, Martinez-Vicente M, Krüger U, Kaushik S, Wong E, Mandelkow EM, Cuervo AM, Mandelkow E (2009) Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum Mol Genet 18(21):4153–4170
Wang HC, Zhang T, Kuerban B, Jin YL, Le W, Hara H, Fan DS, Wang YJ, Tabira T, Chui DH (2015a) Autophagy is involved in oral rAAV/Aβ vaccine-induced Aβ clearance in APP/PS1 transgenic mice. Neurosci Bull 31(4):491–504
Wang T, Martin S, Papadopulos A, Harper CB, Mavlyutov TA, Niranjan D, Glass NR, Cooper-White JJ, Sibarita JB, Choquet D, Davletov B, Meunier FA (2015b) Control of autophagosome axonal retrograde flux by presynaptic activity unveiled using botulinum neurotoxin type a. J Neurosci 35(15):6179–6194
Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A, Pask D, Goldsmith P, O’Kane CJ, Floto RA, Rubinsztein DC (2008) Novel targets for Huntington’s disease in an mTOR-independent autophagy pathway. Nat Chem Biol 4:295–305
Wu T, Wang MC, Jing L, Liu ZY, Guo H, Liu Y, Bai YY, Cheng YZ, Nan KJ, Liang X (2015) Autophagy facilitates lung adenocarcinoma resistance to cisplatin treatment by activation of AMPK/mTOR signaling pathway. Drug Des Devel Ther 9:6421–6431
Xie Y, Zhou B, Lin MY, Sheng ZH (2015) Progressive endolysosomal deficits impair autophagic clearance beginning at early asymptomatic stages in fALS mice. Autophagy 11(10):1934–1936
Yadav RB, Burgos P, Parker AW, Iadevaia V, Proud CG, Allen RA, O’Connell JP, Jeshtadi A, Stubbs CD, Botchway SW (2013) mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging. BMC Cell Biol 14:3
Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, LeeJH Mohan PS, Mercken M, Farmery MR, Tjernberg LO, Jiang Y, Duff K, Uchiyama Y, Näslund J, Mathews PM, Cataldo AM, Nixon RA (2005) Macroautophagy: a novel beta-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol 171:87–98
Yu J, Sun M, Chen Z, Lu J, Liu Y, Zhou L, Xu X, Fan D, Chui D (2010) Magnesium modulates amyloid-beta protein precursor trafficking and processing. J Alzheimers Dis 20(4):1091–1106
Yu Y, Zhou L, Sun M, Zhou T, Zhong K, Wang H, Liu Y, Liu X, Xiao R, Ge J, Tu P, Fan DS, Lan Y, Hui C, Chui D (2012) Xylocoside G reduces amyloid-β induced neurotoxicity by inhibiting NF-κB signaling pathway in neuronal cells. J Alzheimer’s Dis 30(2):263–275
Zhang YD, Zhao JJ (2015) TFEB participates in the Aβ-induced pathogenesis of Alzheimer’s disease by regulating the autophagy-lysosome pathway. DNA Cell Biol 34(11):661–668
Zhou F, van Laar T, Huang H, Zhang L (2011) APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells. Protein Cell 2(5):377–383
Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM (2011) mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 334(6056):678–683
Author information
Authors and Affiliations
Corresponding author
Additional information
Qian Li and Yi Liu have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Li, Q., Liu, Y. & Sun, M. Autophagy and Alzheimer’s Disease. Cell Mol Neurobiol 37, 377–388 (2017). https://doi.org/10.1007/s10571-016-0386-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-016-0386-8