The role of autophagy in supporting cellular survival and inhibiting neurodegeneration in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, which are accompanied by the accumulation of the proteins β-amyloid, α-synuclein, and huntingtin, is discussed. Autophagy undergoes various degrees of weakening in these diseases, and also decreases in aging. Removal of accumulated toxic proteins and structures is mediated by the mechanisms of autophagy (chaperone-mediated autophagy, macroautophagy, mitophagy) in interactions with the ubiquitin-proteasome system. In many cases, activation of mTOR-dependent autophagy and mTOR-independent pathways for its regulation leads to the therapeutic effect of inhibiting neurodegeneration in cell cultures and animal models of diseases. A number of autophagy activators (resveratrol, metformin, rilmenidine, lithium, cucurmin, etc.) are in the stage of clinical trials.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abrahamsen, H., Stenmark, I. L., and Platta, H. W., “Ubiquitination and phosphorylation of Beclin 1 and its binding partners: Tuning class III phosphatidylinositol 3-kinase activity and tumor suppression,” FEBS Lett., 586, 1584–1591 (2012).
Aharon-Peretz, J., Rosenbaum, H., and Gershoni-Baruch, R., “Mutations in the glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews,” New Engl. J. Med., 351, 1972–1977 (2004).
Ahmed, I., Liang, Y., Schools, S., et al., “Development and characterization of a new Parkinson’s disease model resulting from impaired autophagy,” J. Neurosci., 32, 16,503–16,509 (2012).
Alvarez-Erviti, L., Rodriguez-Oroz, M. C., Cooper, J. M., et al., “Chaperone-mediated autophagy markers in Parkinson disease brains,” Arch. Neurol., 67, 1464–1472 (2010).
Alvarez-Erviti, L., Seow, Y., Schapira, A. H., et al., “Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission,” Neurobiol. Dis., 42, No. 3, 360–367 (2011).
Arrasate, M., Mitr, S., Schweitzer, F. S., et al., “Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death,” Nature, 431, 805–810 (2004).
Baba, M., Nakajo, S., Tu, P. H., et al., “Aggregation of α-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies,” Am. J. Pathol., 152, 879–884 (1998).
Balgi, A. D., Fonseca, B. D., Donohue, E., et al., “Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORCI signaling,” PloS One, 4, No. 9, e7124 (2009).
Ballabio, A., “The awesome lysosome,” EMBO Mol. Med., 8, No. 2, 73–76 (2016).
Bartlett, B. J., Isakson, P., Lewerenz, J., et al., “p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects,” Autophagy, 7, No. 6, 572–583 (2011).
Bedford, L., Hay, D., Devoy, A., et al., “Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies,” J. Neurosci., 28, 8189–8198 (2008).
Behrends, C. and Fulda, S., “Receptor proteins in selective autophagy,” Int. J. Cell Biol., 2012, 673290 (2012).
Bento, C. F., Renna, M., Ghislat, G., et al., “Mammalian Autophagy: how does it work?” Annu. Rev. Biochem., 85, No. 1, (2016).
Berger, Z., Ravikumar, B., Menzies, F. M., et al., “Rapamycin alleviates toxicity of different aggregate-prone proteins,” Hum. Mol. Genet., 15, 433–42 (2006).
Boland, B., Kumar, A., Lee, S., et al., “Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease,” J. Neurosci., 28, 6926–6937 (2008).
Bove, J., Martinez-Vicente, M., and Vila, M., “Fighting neurodegeneration with rapamycin: mechanistic insights,” Nat. Rev. Neurosci., 12, 437–452 (2011).
Boya, P., González-Polo, R. A., Casares, N., et al., “Inhibition of macroautophagy triggers apoptosis,” Mol. Cell., Biol., 25, No. 3, 1025–1040 (2005).
Bürli, R. W., Luckhurst, C. A., Aziz, O., et al., “Design, synthesis, and biological evaluation of potent and selective class IIa histone deacetylase (HDAC) inhibitors as a potential therapy for Huntington’s disease,” J. Med. Chem., 56, No. 24, 9934–54 (2013).
Butiner, S., Broeskamp, E., Sommer, C., et al., “Spermidine protects against α-synuclein neurotoxicity,” Cell Cycle, 13, 3903–3908 (2014).
Button, R. W., Luo, S., and Rubinsztein, D. C., “Autophagic activity in neuronal cell death,” Neurosci. Bull., 31, No. 4, 382–394 (2015).
Caccamo, A., Majuder, S., Richardson, A., et al., “Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-5, and Tau: Effects on cognitive impairments,” J. Biol. Chem., 285, 13107–13120 (2010).
Cataldo, A. M., Mathews, P. M., Boiteau, A. B., et al., “Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects,” Am. J. Pathol., 173, 370–384 (2008).
Ciechanover, A. and Kwon, Y., T., “Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies,” Exp. Mol. Med., 47, e147 (2015).
Chauhan, S., Goodwin, J. G., Chauhan, S., et al., “ZKSCAN3 is a master transcriptional repressor of autophagy,” Mol. Cell., 50, 16–28 (2013).
Chen, H. C., Fong, T. K., Hsu, P. W., and Chiu, W. T., “Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion, antiinflammation, and neuroprotection,” J. Surg. Res., 179, No. 1, e203–e210 (2013).
Cheung, T., Zhang, N. Q., Hung, C. H., et al., “Temporal relationship of autophagy and apoptosis in neurons challenged by low molecular weight β-amyloid peptide,” J. Cell Mol. Med., 15, No. 2, 244–57 (2011).
Choudhury, S., Kolukula V. K., Preet, A., et al., “Dissecting the pathways that destabilize mutant p53, the proteasome or autophagy?” Cell Cycle, 12, 1022–1029 (2013).
Chu, C. T., “Autophagic stress in neuronal injury and disease,” J. Neuropathol. Exp. Neurol., 65, 423–432 (2006).
Chu, Y., Dodiya, H., Aebischer, P., et al., “Alterations in lysosomal and proteasomal markers in Parkinson’s disease: relationship to α-synuclein inclusions,” Neurobiol. Dis., 35, 385–398 (2009).
Coune, P. G., Bensadoun, J. C., Aebischer, P., and Schneider, B. L., “Rab1A over-expression prevents Golgi apparatus fragmentation and partially corrects motor deficits in an alpha-synuclein based rat model of Parkinson’s disease,” J. Parkinsons Dis., 1, 373–387 (2011).
Crews, L., Spencer, B., Desplats, P., et al., “Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy,” PLoS One, 5, No. 2, e9313 (2010).
Cuervo, A. M., “Autophagy: many paths to the same end,” Mol. Cell. Biochem., 263, No. 1–2, 55–72 (2004).
Cuervo, A. M., Stefanis, L., Fredenburg, R., et al., “Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy,” Science, 305, 1292–1295 (2004).
Cuervo, A. M. and Wong, E., “Chaperone-mediated autophagy: roles in disease and aging,” Cell. Res., 24, No. 1, 92–104 (2014).
Cullen, V., Sardi, S. P., Ng, J., et al., “Acid β-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing,” Ann. Neurol., 69, No. 6, 940–953 (2011).
Dantuma, N. P. and Lindsten, K., “Stressing the ubiquitin-proteasome system,” Cardiovasc. Res., 85, No. 2, 263–271 (2010).
Das, G., and Shravage, B. V., and Baehrecke, E. H., “Regulation and function of autophagy during cell survival and cell death,” Cold Spring Harb. Perspect. Biol., 4, No. 6, pii: a008813 (2012).
Decressac, M., Mattsson, B., Weikop, P., et al., “TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity,” Proc. Natl. Acad. Sci. USA, 110, E1817–E1826 (2013).
Dehay, B., Bove, J., Rodriguez-Muela, N., et al., “Pathogenic lysosomal depletion in Parkinson’s disease,” J. Neurosci., 30, No. 37, 12535–12544 (2010).
Dehay, B., Ramirez, A., Martinez-Vicente, M., et al., “Loss of P-type ATPase ATP13A2/PARK9 function induces general lysosomal defi - ciency and leads to Parkinson disease neurodegeneration,” Proc. Natl. Acad. Sci. USA, 109, No. 24, 9611–9616 (2012).
Demuro, A., Mina, E., Kayed, R., et al., “Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers,” J. Biol. Chem., 280, 17,294–17,300 (2005).
Deng, Y. N., Shi, J., Liu, J., and Qu, Q. M., “Celastrol protects human neuroblastoma SH-SY5Y cells from rotenone-induced injury through induction of autophagy,” Neurochem. Int., 63, 1–9 (2013).
Dennissen, E. J., Kholod, N., and van Leeuwen, E. W., “The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim?” Prog. Neurobiol, 96, 190–207 (2012).
Di Zanni, E., Bachetti, T., Parodi, S., et al., “In vitro drug treatments reduce the deleterious effects of aggregates containing polyAla expanded PHOX2B proteins,” Neurobiol. Dis., 45, No. 1, 508–518 (2012).
Diaz-Hernandez, M., Valera, A. G., Moran, M. A., et al., “Inhibition of 26S proteasome activity by huntingtin fi laments but not inclusion bodies isolated from mouse and human brain,” J. Neurochem., 98, No. 5, 1585–1596 (2006).
Dice, J. E., “Chaperon-mediated autophagy,” Autophagy, 3, 295–299 (2007).
Ding, W. X., and Yin, X. M., “Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome,” Autophagy, 4, 141–150 (2008).
Du, G., Liu, X., Chen, X., et al., “Drosophila histone deacetylase 6 protects dopaminergic neurons against α-synuclein toxicity by promoting inclusion formation,” Mol. Biol. Cell., 21, 2128–2137 (2010).
Dupuis, L., “Mitochondrial quality control in neurodegenerative diseases,” Biochimie, 100, 177–183 (2014).
Ebrahimi-Fakhari, D., Cantuti-Castelvetri, I., Fan, Z., et al., “Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of alpha-synuclein,” J. Neurosci., 31, No. 41, 14,508–14,520 (2011).
Feldman, M. E., Apsel, B., Uotila, A., et al., “Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2,” PLoS Biol., 7, No. 2, e38 (2009).
Filimonenko, M., Isakson, P., Finley, K. D., et al., “The selective macroautophagic degradation of aggregated proteins requires the PI3Pbinding protein Alfy,” Mol. Cell., 38, No. 2, 265–279 (2010).
Filomeni, G., Graziani, L., De Zio, D., et al., “Neuroprotection of kaempferol by autophagy in models of rotenone mediated acute toxicity: possible implications for Parkinson’s disease,” Neurobiol. Aging, 33, No. 4, 767–785 (2012).
Floto, R. A., Sarkar, S., Perlstein, E. O., et al., “Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington’s disease models and enhance killing of mycobacteria by macrophages,” Autophagy, 3, No. 6, 620–622 (2007).
Forlenza, O. V., De Paula, V. J., Machado-Vieira, R., et al., “Does lithium prevent Alzheimer’s disease?” Drugs Aging, 29, 335–342 (2012).
Frake, R. A., Ricketts, T., Menzies, F. M., and Rubinsztein, D. C., “Autophagy and neurodegeneration,” J. Clin. Invest., 125, 65–74 (2015).
Fusco, C., Micale, L., Egorov, M., et al., “The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome,” PLoS One, 7, No. 7, e40440 (2012).
Gal, J., Ström, A. L., Kwinter, D. M., et al., “Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism,” J. Neurochem., 111, No. 4, 1062–1073 (2009).
Galluzzi, L., Vitale, L., Abrams, J. M., et al., “Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death,” Cell Death Differ., 19, No. 1, 107–120 (2012).
Geisler, S., Holmstrom, K. M., Skteat, D., et al., “PINKI/Parkin mediated mitophagy is dependent on VDAC1 and p62/SQSTMI,” Nat. Cell. Biol., 12, 119–131 (2010).
Ghavami, S., Shojaei, S., Yeganeh, B., et al., “Autophagy and apoptosis dysfunction in neurodegenerative disorders,” Prog. Neurobiol., 112, 24–49 (2014).
Hamano, T., Gendron, T. E., Causevic, E., et al., “Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression,” Eur. J. Neurosci., 27, No. 5, 1119–1130 (2008).
Hara, T., Nakamura, K., Matsui, M., et al., “Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice,” Nature, 441, No. 7095, 885–889 (2006).
Hashemi, M., Ghavami, S., Eshraghi, M., et al., “Cytotoxic effects of intra and extracellular zinc chelation on human breast cancer cells,” Eur. J. Pharmacol., 557, No. 1, 9–19 (2007).
Hashimoto, M., Rockenstein, E., Crews, L., and Masliah, E., “Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases,” Neuromolecular Med., 4, No. 1–2, 21–36 (2003).
He, L. Q., Lu, J. H., and Yue, Z. Y., “Autophagy in ageing and ageing associated diseases,” Acta Pharmacol. Sin., 34, No. 5, 605–611 (2013).
Hegde, A. N. and Upadhya, S. C., “Role of ubiquitin-proteasome mediated proteolysis in nervous system disease,” Biochim. Biophys. Acta, 1809, 128–140 (2011).
Hernandez, D., Torres, C. A., Setlik, W., et al., “Regulation of presynaptic neurotransmission by macroautophagy,” Neuron, 74, No. 2, 277–284 (2012).
Hou, W., Han, J., Lu, C., et al., “Autophagic degradation of active caspase-8, a crosstalk mechanism between autophagy and apoptosis,” Autophagy, 6, 891–900 (2010).
Huang, Y. and Mucke, L., “Alzheimer mechanisms and therapeutic strategies,” Cell, 148, 1204–1222 (2012).
Ichimura, Y., Kumanomidou, T., Sou, Y. S., et al., “Structural basis for sorting mechanism of p62 in selective autophagy,” J. Biol. Chem., 283, No. 33, 22847–22857 (2008).
Jiang, T., Yu, J. T., Tian, Y., and Tan, L., “Epidemiology and etiology of Alzheimer’s disease: from genetic to non-genetic factors,” Curr. Alzheimer Res., 10, 852–867 (2013a).
Jiang, T. E., Zhang, Y. J., Zhou, H. Y., et al., “Curcumin ameliorates the neurodegenerative pathology in A53T cc-synuclein tell model of Parkinson’s disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy,” J. Neuroimmune Pharmacol., 8, No. 1, 356–369 (2013b).
Johnson, G. W., Melia, T. I., and Yamamoto, A., “Modulating macroautophagy: a neuronal perspective,” Future Med. Chem., 4, 1715–1731 (2012).
Kang, C. and Avery, L., “To be or not to be, the level of autophagy is the question: dual roles of autophagy in the survival response to starvation,” Autophagy, 4, 82–84 (2008).
Kaushik, S., Massey, A. C., Mizushima, N., and Cuervo, A. M., “Constitutive activation of chaperone-mediated autophagy in tells with impaired macroautophagy,” Mol. Biol. Cell., 19, 2179–2192 (2008).
Keller, J. N., Huang, E. E., and Markesbery, W. R., “Decreased levels of pro te asome activity and proteasome expression in aging spinal cord,” Neuroscience, 98, 149–156 (2000).
Kempermann, G., “Activity dependency and aging in the regulation of adult neurogenesis,” Cold Spring Harb. Perspect. Biol., 7, No. 11 (2015); pii: a018929
Khan, M. M., Ahmad, A., Ishrat, T., et al., “Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson’s disease,” Brain Res., 1328, 139–151 (2010).
Kickstein, E., Krauss, S., Thornhill, P., et al., “Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling,” Proc. Natl. Acad. Sci. USA, 107, No. 50, 21,830–21,835 (2010).
Kiffin, R., Christian, C., Knecht, E., and Cuervo, A. M., “Activation of chaperone-mediated autophagy during oxidative stress,” Mol. Biol. Cell., 15, 4829–4840 (2004).
Kim, D., Nguyen, M. D., Dobbin, M. M., et al., “SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis,” EMBO J., 26, No. 13, 3169–3179 (2007).
Kim, J., Kundu, M., Viollet, B., and Guan, K. L., “AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1,” Nat. Cell. Biol., 13, 132e141 (2011).
Kiriyama, Y. and Nochi, H., “The function of autophagy in neurodegenerative diseases,” Int. J. Mol. Sci., 16, No. 11, 26797–26812 (2015).
Kirkin, V. T., Lamark, Y. S., Sou, G., et al., “A role for NBR1 in autophagosomal degradation of ubiquitinated substrates,” Mol. Cell., 33, 505–516 (2009).
Klionsky, D. J., Abdelmohsen, K., Abe, A., et al. (more than 2000 co-authors), “Guidelines for the use and interpretation of assays for monitoring autophagy (3rd ed.),” Autophagy, 12, No. 1, 1–222 (2016).
Kochergin, I. A. and Zakharova, M. N., “The role of autophagy in neurodegenerative diseases,” Neirokhimiya, 33, No. 1, 12–24 (2016).
Koga, H., Martinez-Vicente, M., Arias, et al., “Constitutive upregulation of chaperone-mediated autophagy in Huntington’s disease,” J. Neurosci., 31, No. 50, 18492–18505 (2011).
Komatsu, M., Waguri, S., Chiba, T., et al., “Loss of autophagy in the central nervous system causes neurodegeneration in mice,” Nature, 441, No. 7095, 880–884 (2006).
Komatsu, M., Wang, Q. J., Holstein, G. R., et al., “Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration,” Proc. Natl. Acad. Sci. USA, 104, No. 36, 14489–14494 (2007).
Korolchuk, V. I., Menzies, F. M., and Rubinsztein, D. C., “Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems,” FEBS Lett., 584, No. 7, 1393–1398 (2010).
Larsen, K. E. and Sulzer, D., “Autophagy in neurons: a review,” Histol. Histopathol., 17, 897–908 (2002).
Lazzara, C. A. and Kim, Y. H., “Potential application of lithium in Parkinson’s and other neurodegenerative diseases,” Front. Neurosci., 9, 403 (2015).
Lee, J.-H., Yu, W. H., Kumar, A., et al., “Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations,” Cell, 141, No. 7, 1146–1158 (2010a).
Lee, J. Y., Koga, H., Kawaguchi, Y., et al., “HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy,” EMBO J., 29, No. 5, 969–980 (2010b).
Lee, M. J., Lee, J. H., and Rubinsztein, D. C., “Tau degradation: the ubiquitin-proteasome system versus the autophagolysosome system,” Prog. Neurobiol., 105, 49–59 (2013).
Lee, S., Sato, Y., and Nixon, R. A., “Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer’s-like axonal dystrophy,” J. Neurosci., 31, No. 21, 7817–7830 (2011).
Li, L., Zhang, S., Zhang, X., et al., “Autophagy enhancer carbamazepine alleviates memory deficits and cerebral amyloid-beta pathology in a mouse model of Alzheimer’s disease,” Curr. Alzheimer Res., 10, 433e441 (2013).
Liang, Q. L., Ouyang, X. S., Schneider, L., and Zhang, J. H., “Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons,” Mol. Neurodegener., 6, 37 (2011).
Lin, T. K., Chen, S. D., Chuang, Y. C., et al., “Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy,” Int. J. Mol. Sci., 15, 1625–1646 (2014).
Lindersson, E., Beedholm, R., Hojrup, P., et al., “Proteasomal inhibition by alpha-synuclein fi laments and oligomers,” J. Biol. Chem., 279, No. 13, 12924–12934 (2004).
Lipinski, M. M., Zheng, B., Lu, T., et al., “Genome-wide analysis reveals me chanisms modulating autophagy in normal brain aging and in Alzheimer’s disease,” Proc. Natl. Acad. Sci. USA, 107, No. 32, 14164–14169 (2010).
Liu, C. W., Corboy, M. J., DeMartino, G. N., and Thomas, P. J., “Endoproteolytic activity of the proteasome,” Science, 299, 408–411 (2003).
Liu, D., Pitta, M., Jiang, H., et al., “Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession,” Neurobiol. Aging, 34, 1564–1580 (2013).
Lu, K., Psakhye, I., and Jentsch, S., “Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family,” Cell, 158, 549–563 (2014).
Lynch-Day, M. A., Mao, K., Wang, K., et al., “The role of autophagy in Parkinson’s disease,” Cold Spring Harb. Perspect. Med., 2, a009357 (2012).
Ma, Q., Qiang, J., Gu, P., et al., “Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice,” Exp. Gerontol., 46, 533e541 (2011).
Ma, T. C., Buescher, J. L., Oatis, B., et al., “Metformin therapy in a transgenic mouse model of Huntington’s disease,” Neurosci. Lett., 411, No. 2, 98–103 (2007).
Maday, S., Wallace, K. E., and Holzbaur, E. L. F., “Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons,” J. Cell Biol., 196, No. 4, 407–417 (2012).
Magnaudeix, A., Wilson, C. M., Page, G., et al., “PP2A blockade inhibits autophagy and causes intraneuronal accumulation of ubiquitinated proteins,” Neurobiol. Aging, 34, No. 3, 770–790 (2013).
Majumder, S., Richardson, A., Strong, R., and Oddo, S., “Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits,” PLoS One, 6, e25416 (2011).
Malagelada, C., Jin, Z. H., Jackson-Lewis, V., et al., “Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson’s disease,” J. Neurosci., 30, 1166–1175 (2010).
Mandell, M. A., Jain, A., Arko-Mensah, J., et al., “TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition,” Dev. Cell, 30, No. 4, 394–409 (2014).
Marambaud, P., Zhao, H., and Davies, P., “Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides,” J. Biol. Chem., 280, 37377–37382 (2005).
Martin, D. D., Ladha, S., Ehrnhoefer, D. E., and Hayden, M. R., “Autophagy in Huntington disease and huntingtin in autophagy,” Trends Neurosci., 38, 26–35 (2015).
Martinez-Vicente, M., Talloczy, Z., Kaushik, S., et al., “Dopamine-mo dified α-synuclein blocks chaperon-mediated autophagy,” J. Clin. Invest., 118, No. 2, 777–788 (2008).
Martinez-Vicente, M., Talloczy, Z., Wong, E., et al., “Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease,” Nat. Neurosci., 13, 567–576 (2010).
Martinez-Vicente, M., “Autophagy in neurodegenerative diseases: from pathogenic dysfunction to therapeutic modulation,” Semin. Cell Dev. Biol., 40, 115–126 (2015).
Martinez-Vicente, M. and Vila, M., “Alpha-synuclein and protein degradation pathways in Parkinson’s disease: a pathological feed-back loop,” Exp. Neurol., 247, 308–313 (2013).
Martini-Stoica, H., Xu, Y., Ballabio, A., and Zheng, H., “The Autophagy-Lysosomal Pathway in Neurodegeneration: A TFEB Perspective,” Trends Neurosci., pii: S01662236(16)00026-6 (2016).
Matsumoto, G., Wada, K., Okuno, M., et al., “Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins,” Mol. Cell., 44, 279–289 (2011).
Mazzulli, J. R., Xu, Y. H., Sun, Y., et al., “Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies,” Cell, 146, No. 1, 37–52 (2011).
McNaught, K. S. and Jenner, P., “Proteasomal function is impaired in substantia nigra in Parkinson’s disease,” Neurosci. Lett., 297, 191–194 (2001).
Mealer, R. G., Murray, A. J., Shahani, N., et al., “Rhes, a striatal-selective protein implicated in Huntington disease binds beclin-1 and activates autophagy,” J. Biol. Chem., 289, 3547–3554 (2014).
Mendelsohn, A. R. and Larrick, J. W., “Rapamycin as an antiaging therapeutic?: targeting mammalian target of rapamycin to treat Hutchinson-Gilford progeria and neurodegenerative diseases,” Rejuvenation Res., 14, 437–441 (2011).
Menzies, E. M., Huebener, J., Renna, M., et al., “Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3,” Brain, 133, No. Pt 1, 93–104 (2010).
Mizushima, N., Yamamoto, A., Matsui, M., et al., “In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker,” Mol. Biol. Cell., 15, 1101–1111 (2004).
Mizushima, N., “The role of the Atg1/ULK1 complex in autophagy regulation,” Curr. Opin. Cell Biol., 22, 132–139 (2010).
Munoz-Sanjuan, L. and Bates, G. P., “The importance of integrating basic and clinical research toward the development of new therapies for Huntington disease,” J. Clin. Invest., 121, 476–483 (2011).
Nah, J., Yuan, J., and Jung, Y. K., “Autophagy in neurodegenerative diseases: from mechanism to therapeutic approach,” Mol. Cells, 38, No. 5, 381–389 (2015).
Narendra, D., Tanaka, A., Suen, D. E., and Youle, R. J., “Parkin is recruited selectively to impaired mitochondria and promotes their autophagy,” J. Cell Biol., 183, No. 5, 795–803 (2008).
Nijholt, D. A. T., De Kimpe, L., Elfrink, H. L., et al., “Removing protein aggregates: the role of proteolysis in neurodegeneration,” Curr. Med. Chem., 18, No. 16, 2459–2476 (2011).
Nikoletopoulou, V., Papandreou, M., and Tavernarakis, N., “Autophagy in the physiology and pathology of the central nervous system,” Cell Death Differ., 22, No. 3, 398–407 (2015).
Nixon, R. A. and Yang, D. S., “Autophagy failure in Alzheimer’s diseased locating the primary defect,” Neurobiol. Dis., 43, 38–45 (2011).
Ochaba, J., Lukacsovich, T., Csikos, G., et al., “Potential function for the Huntingtin protein as a scaffold for selective autophagy,” Proc. Natl. Acad. Sci. USA, 111, No. 47, 16889–16894 (2014).
Olzmann, J. A. and Chin, L. S., “Parkin-mediated K63-linked polyubiquitination: a signal for targeting misfolded proteins to the aggresome-autophagy pathway,” Autophagy, 4, 85–87 (2008).
Opipari, A. W., Jr., Tan, L., Boitano, A. E., et al., “Resveratrol-induced autophagocytosis in ovarian cancer tells,” Cancer Res., 64, No. 2, 696–703 (2004).
Orenstein, S. J. and Cuervo, A. M., “Chaperone-mediated autophagy: molecular mechanisms and physiological relevance,” Semin. Cell. Dev. Biol., 21, No. 7, 719–726 (2010).
Pankiv, S., Clausen, T. H., Lamark, T., et al., “p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy,” J. Biol. Chem., 282, 24131–24145 (2007).
Paxinou, E., Chen, Q., Weisse, M., et al., “Induction of α-synuclein aggregation by intracellular nitrative insult,” J. Neurosci., 21, No. 20, 8053–8061 (2001).
Petherick, K. J., Williams, A. C., Lane, I. D., et al., “Autolysosomal 13-catenin degradation regulates Wnt-autophagy-p62 crosstalk,” EMBO J., 32, 1903–1916 (2013).
Petrucelli, L., Dickson, D., Kehoe, K., et al., “CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation,” Hum. Mol. Genet., 13, No. 7, 703–714 (2004).
Pickford, E., Masliah, E., Britschgi, M., et al., “The autophagy related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice,” J. Clin. Invest., 118, 2190–2199 (2008).
Pivtoraiko, V. N., Harrington, A. J., Mader, B. J., et al., “Low-dose bafi lomycin attenuates neuronal tell death associated with autophagy-lysosome pathway dysfunction,” J. Neurochem., 114, No. 4, 1193–1204 (2010).
Polito, V. A., Li, H., Martini-Stoica, H., et al., “Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB,” EMBO Mol. Med., 6, No. 9, 1142–1160 (2014).
Qi, L., Zhang, X. D., Wu, J. C., et al., “The role of chaperon-mediated autophagy in huntingtin degradation,” PLoS One, 7, e46834 (2012).
Qin, Z. H., Wang, Y. M., Kegel, K. B., et al., “Autophagy regulates the processing of amino terminal huntingtin fragments,” Hum. Mol. Genet., 12, 3231–3244 (2003).
Ravid, T. and Hochstrasser, M., “Diversity of degradation signals in the ubiquitin-proteasome system,” Nat. Rev. Mol. Cell. Biol., 9, No. 9, 679–690 (2008).
Ravikumar, B., Sarkar, S., Davies, I. E., et al., “Regulation of mammalian autophagy in physiology and pathophysiology,” Physiol. Rev., 90, No. 4, 1383–1435 (2010).
Ravikumar, B., Vacher, C., Berger, Z., et al., “Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease,” Nat. Genet., 36, No. 6, 585–595 (2004).
Recasens, A. and Dehay, B., “Alpha-synuclein spreading in Parkinson’s disease,” Front. Neuroanat., 8, 159 (2014).
Richter-Landsberg, C. and Leyk, J., “Inclusion body formation, macroautophagy, and the role of HDAC6 in neurodegeneration,” Acta Neuropathol., 126, No. 6, 793–807 (2013).
Rodriguez-Gonzalez, A., Lin, T., Ikeda, A. K., et al., “Role of the aggresome pathway in cancer: targeting histone deacetylase 6-dependent protein degradation,” Cancer Res., 68, 2557–2560 (2008).
Rodriguez-Navarro, J. A. and Cuervo, A. M., “Autophagy and lipids: tightening the knot,” Semin. Immunopathol., 32, 343–353 (2010).
Rodríguez-Navarro, J. A., Rodriguez, L., Casarejos, M. J., et al., “Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation,” Neurobiol. Dis., 39, No. 3, 423–438 (2010).
Rogov, V., Dotsch, V., Johansen, T., and Kirkin, V., “Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy,” Mol. Cell., 53, No. 2, 167–178 (2014).
Rohn, T. T., Wirawan, E., Brown, R. I., et al., “Depletion of Beclin-1 due to proteolytic cleavage by caspases in the Alzheimer’s disease brain,” Neurobiol. Dis., 43, 68–78 (2011).
Rose, C., Menzies, F. M., Renna, M., et al., “Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington’s disease,” Hum. Mol. Genet., 19, 2144–2153 (2010).
Rubinsztein, D. C., “The roles of intracellular protein degradation pathways in neurodegeneration,” Nature, 43, No. 7113, 780–786 (2006).
Rubinsztein, D. C., Marino, G., and Kroemer, G., “Autophagy and aging,” Cell, 146, 682–695 (2011).
Sarkar, S., “Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers,” Biochem. Soc. Trans., 41, 1103–1130 (2013).
Sarkar, S., Davies, J. E., Huang, Z., et al., “Trehalose, a novel mTOR independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein,” J. Biol. Chem., 282, 5641–5652 (2007).
Sarkar, S., Floto, R. A., Berger, Z., et al., “Lithium induces autophagy by inhibiting inositol monophosphatase,” J. Cell Biol., 170, 1101e1111 (2005).
Sarkar, S., Krishna, G., Imarisio, S., et al., “A rational mechanism for combination treatment of Huntington’s disease using lithium and rapamycin,” Hum. Mol. Genet., 17, 170–178 (2008).
Schreiber, A. and Peter, M., “Substrate recognition in selective autophagy and the ubiquitin-proteasome system,” Biochem. Biophys. Acta, 1843, No. 1, 163–181 (2013).
Seidel, K., Schöls, L., Nuber, S., et al., “First appraisal of brain pathology owing to A30P mutant alpha-synuclein,” Ann. Neurol., 67, 684–689 (2010).
Settembre, C., Di Malta, C., Polito, et al., “TFEB links autophagy to lysosomal biogenesis,” Science, 332, No. 6036, 1429–1433 (2011).
Sidransky, E., Nails, M. A., Aasly, J. O., et al., “Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease,” New Engl. J. Med., 361, No. 17, 1651–1661 (2009).
Sharma, K., Le, N., Alotaibi, M., and Gewirtz, D. A., “Cytotoxic autophagy in cancer therapy,” Int. J. Mol. Sci., 15, 10034–10051 (2014).
Shen, H. M., and Codogno, P., “Autophagic cell death: Loch Ness monster or endangered species?” Autophagy, 7, No. 5, 457–465 (2011).
Shen, Y. F., Tang, Y., Zhang, X. J., et al., “Adaptive changes in autophagy after UPS impairment in Parkinson’s disease,” Acta Pharmacol. Sin., 34, 667–673 (2013).
Shibata, M., Lu, T., Furuya, T., et al., “Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1,” J. Biol. Chem., 281, 14474–14485 (2006).
Shimizu, S., Kanaseki, T., Mizushima, N., et al., “Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes,” Nat. Cell. Biol., 6, No. 12, 1221–1228 (2004).
Shoji-Kawata, S., Sumpter, R., Leveno, M., et al., “Identification of a candidate therapeutic autophagy inducing peptide,” Nature, 494, No. 7436, 201–206 (2013).
Singh, S. K., Srivastav, S., Yadav, A. K., et al., “Overview of Alzheimer’s disease and some therapeutic approaches targeting Aβ by using several synthetic and herbal compounds,” Oxid. Med. Cell. Longev., 2016, 7361613 (2016).
Singleton, A. B., Farrer, M., Johnson, J., et al., “α-Synuclein locus triplication causes Parkinson’s disease,” Science, 302, No. 5646, 841 (2003).
Smaili, S. S., Ureshino, R. P., Rodrigues, L., et al., “The role of mitochondrial function in glutamate-dependent metabolism in neuronal cells,” Curr. Pharm. Des., 17, 3865–3877 (2011).
Spencer, B., Potkar, R., Trejo, M., et al., “Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in α-synuclein models of Parkinson’s and Lewy body diseases,” J. Neurosci., 29, 13,578–13,588 (2009).
Spilman, P., Podlutskaya, N., Hart, M. J., et al., “Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-13 levels in a mouse model of Alzheimer’s disease,” PLoS One, 5, No. 4, e9979 (2010).
Steele, J. W. and Gandy, S., “Latrepirdine (Dimebon®), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model,” Autophagy, 9, 617–618 (2013).
Sulzer, D., Mosharov, E., Talloczy, Z., et al., “Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease,” J. Neurochem., 106, No. 1, 24–36 (2008).
Tai, H. C., Serrano-Pozo, A., Hashimoto, T., et al., “The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system,” Am. J. Pathol., 181, 1426–1435 (2012).
Tan, C. C., Yu, J. T., Tan, M. S., et al., “Autophagy in aging and neuro-degenerative diseases: implications for pathogenesis and therapy,” Neurobiol. Aging, 35, No. 5, 941–957 (2014).
Tanaka, M., Machida, Y., Niu, S., et al., “Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease,” Nat. Med., 10, 148–154 (2004).
Taylor, R. C. and Dillin, A., “Aging as an event of proteostasis collapse,” Cold Spring Harb. Perspect. Biol., 3, No. 5 (2011); pii: a004440
Thompson, L. M., Aiken, C. T., Kaltenbach, L. S., et al., “IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome,” J. Cell Biol., 187(7), 1083–1099 (2009).
Thoreen, C. C., Kang, S. A., Chang, J. W., et al., “An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1,” J. Biol. Chem., 284, 8023–8032 (2009).
Thurston, T. L., Wandel, M. P., von Muhlinen, N., et al., “Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion,” Nature, 482, 414–418 (2012).
Tian, Y., Bustos, V., Flajolet, M., and Greengard, P., “A small molecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway,” FASEB J., 25, 1934–1942 (2011).
Tofaris, G. K., Kim, H. T., Hourez, R., et al., “Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway,” Proc. Natl. Acad. Sci. USA, 108, 17004–17009 (2011).
Trimmer, P. A. and Bennett, J. P., Jr., “The cybrid model of sporadic Parkinson’s disease,” Exp. Neurol., 218, 320–325 (2009).
Tsvetkov, A. S., Miller, J., Arrasate, M., et al., “A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model,” Proc. Natl. Acad. Sci. USA, 107, 16982–16987 (2010).
Tsunemi, T., Ashe, T. D., Morrison, B. E., et al., “PGC-1alpha rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function,” Sci. Transl. Med., 4, 142ra197 (2012).
Ulbricht, A., Arndt, V., and Höhfeld, J., “Chaperone-assisted proteostasis is essential for mechanotransduction in mammalian cells,” Commun. Integr. Biol., 6, e24925 (2013).
Underwood, B. R., Imarisio, S., Fleming, A., et al., “Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease,” Hum. Mol. Genet., 19, No. 17, 3413–3429 (2010).
Uversky, V. N., “Neuropathology, biochemistry, and biophysics of α-synuclein aggregation,” J. Neurochem., 103, No. 1, 17–37 (2007).
Vidal, R. L., Matus, S., Bargsted, L., and Hetz, C., “Targeting autophagy in neurodegenerative diseases,” Trends Pharmacol. Sci., 35, No. 11, 583–591 (2014).
Vingtdeux, V., Chandakkar, P., Zhao, H., et al., “Novel synthetic small-molecule activators of AMPK as enhancers of autophagy and amyloid-beta peptide degradation,” FASEB J., 25, 219–231 (2011).
Vingtdeux, V., Giliberto, L., Zhao, H., et al., “AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism,” J. Biol. Chem., 285, 9100–9113 (2010).
Vogiatzi, T., Xilouri, M., Vekrellis, K., and Stefanis, L., “Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells,” J. Biol. Chem., 283, No. 35, 23542–23556 (2008).
Wang, P., Guan, Y. E., Du, H., et al., “Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia,” Autophagy, 8, 77–87 (2012).
Wang, D. W., Peng, Z. I., Ren, G. E., and Wang, G. X., “The different roles of selective autophagic protein degradation in mammalian cells,” Oncotarget, 6, No. 35, 37,098–37,116 (2015).
Wang, P., Li, B., Zhou, L., et al., “The kdel receptor induces autophagy to promote the clearance of neurodegenerative disease-related proteins,” Neuroscience, 190, 43–55 (2011).
Wang, Y., Martinez-Vicente, M., Krüger, U., et al., “Synergy and antagonism of macroautophagy and chaperone-mediated autophagy in a cell model of pathological tau aggregation,” Autophagy, 6, No. 1, 182–183 (2010).
Ward, S. M., Himmelstein, D. S., Lancia, J. K., and Binder, L. I., “Tau oligomers and tau toxicity in neurodegenerative disease,” Biochem. Soc. Trans., 40, 667–671 (2012).
Webb, J. L., Ravikumar, B., Atkins, J., et al., “Alpha-synuclein is degraded by both autophagy and the proteasome,” J. Biol. Chem., 278, 25009–25013 (2003).
Weidberg, H., Shvets, E., and Elazar, Z., “Biogenesis and cargo selectivity of autophagosomes,” Annu. Rev. Biochem., 80, 125–156 (2011).
Wild, P., Farhan, H., McEwan, D. G., et al., “Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth,” Science, 333, No. 6039, 228–233 (2011).
Williams, A., Sarkar, S., Cuddon, P., et al., “Novel targets for Huntington’s disease in an mTOR-independent autophagy pathway,” Nat. Chem. Biol., 4, No. 5, 295305 (2008).
Williams, A. J. and Paulson, H. L., “Polyglutamine neurodegeneration: protein misfolding revisited,” Trends Neurosci., 31, 521–528 (2008).
Winslow, A. R., Chen, C.-W., Corrochano, S., et al., “α-Synuclein impairs macroautophagy: implications for Parkinson’s disease,” J. Cell Biol., 190, No. 6, 1023–1037 (2010).
Wong, K., Sidransky, E., Verma, A., et al., “Neuropathology provides clues to the pathophysiology of Gaucher disease,” Mol. Genet. Metab., 82, No. 3, 192–207 (2004).
Wu, Y., Li, X., Zhu, L. X., et al., “Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease,” Neurosignals, 19, 163–174 (2011).
Xiao, Q., Yan, P., Ma, X., et al., “Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis,” J. Neurosci., 34, No. 29, 9607–9620 (2014).
Xilouri, M., Brekk, O. R., Landeck, N., et al., “Boosting chaperone-mediated autophagy in vivo mitigates α-synuclein-induced neurodegeneration,” Brain, 136, 2130–2146 (2013).
Xilouri, M., Vogiatzi, T., Vekrellis, K., et al., “Aberrant α-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy,” PLoS One, 4, e5515 (2009).
Xilouri, M. and Stefanis, L., “Autophagy in the central nervous system: implications for neurodegenerative disorders,” CNS Neurol. Disord. Drug Targets, 9, No. 6, 701–719 (2010).
Xiong, N., Xiong, J., Jia, M., et al., “The role of autophagy in Parkinson’s disease: rotenone-based modeling,” Behav. Brain Funct., 9, 13 (2013).
Yu, L., McPhee, C. K., Zheng, L., et al., “Termination of autophagy and reformation of lysosomes regulated by mTOR,” Nature, 465, 942–946 (2010).
Yu, S. W., Baek, S. H., Brennan, R. T., et al., “Autophagic death of adult hippocampal neural stem cells following insulin withdrawal,” Stem Cells, 26, No. 10, 2602–2610 (2008).
Yu, W. H., Cuervo, A. M., Kumar, A., et al., “Macroautophagy – a novel β-amyloid peptide-generating pathway activated in Alzheimer’s disease,” J. Cell Biol., 171, No. 1, 87–98 (2005).
Zeigerer, A., Gilleron, J., Bogorad, R. L., et al., “Rab5 is necessary for the biogenesis of the endolysosomal system in vivo,” Nature, 485, 465–70 (2012).
Zhang, L., Sun, Y., Fei, M., et al., “Disruption of chaperone-mediated autophagy-dependent degradation of MEF2A by oxidative stress-induced lysosome destabilization,” Autophagy, 10, 1015–1035 (2014a).
Zhang, X., Chen, S., Song, L., et al., “MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis,” Autophagy, 10, No. 4, 588–602 (2014b).
Zhang, X. J., Chen, S., Huang, K. X., and Le, W. D., “Why should autophagic flux be assessed?” Acta Pharmacol. Sin., 34, 595–599 (2013).
Zhu, Z., Yan, J., Jiang, W., et al., “Arctigenin effectively ameliorates memory impairment in Alzheimer’s disease model mice targeting both beta-amyloid production and clearance,” J. Neurosci., 33, No. 32, 13138–13149 (2013).
Zuccato, C., Valenza, M., and Cattaneo, E., “Molecular mechanisms and potential therapeutical targets in Huntington’s disease,” Physiol. Rev., 90, No. 3, 905–981 (2010).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 66, No. 5, pp. 515–540, September–October, 2016.
Rights and permissions
About this article
Cite this article
Pupyshev, A.B., Korolenko, T.A. & Tikhonova, M.A. A Therapeutic Target for Inhibition of Neurodegeneration: Autophagy. Neurosci Behav Physi 47, 1109–1127 (2017). https://doi.org/10.1007/s11055-017-0519-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-017-0519-7