{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:39:41Z","timestamp":1787506781360,"version":"build-2736575974"},"reference-count":151,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative diseases result in a range of conditions depending on the type of proteinopathy, genes affected or the location of the degeneration in the brain. Proteinopathies such as senile plaques and neurofibrillary tangles in the brain are prominent features of Alzheimer\u2019s disease (AD). Autophagy is a highly regulated mechanism of eliminating dysfunctional organelles and proteins, and plays an important role in removing these pathogenic intracellular protein aggregates, not only in AD, but also in other neurodegenerative diseases. Activating autophagy is gaining interest as a potential therapeutic strategy for chronic diseases featuring protein aggregation and misfolding, including AD. Although autophagy activation is a promising intervention, over-activation of autophagy in neurodegenerative diseases that display impaired lysosomal clearance may accelerate pathology, suggesting that the success of any autophagy-based intervention is dependent on lysosomal clearance being functional. Additionally, the effects of autophagy activation may vary significantly depending on the physiological state of the cell, especially during proteotoxic stress and ageing. Growing evidence seems to favour a strategy of enhancing the efficacy of autophagy by preventing or reversing the impairments of the specific processes that are disrupted. Therefore, it is essential to understand the underlying causes of the autophagy defect in different neurodegenerative diseases to explore possible therapeutic approaches. This review will focus on the role of autophagy during stress and ageing, consequences that are linked to its activation and caveats in modulating this pathway as a treatment.<\/jats:p>","DOI":"10.3390\/ijms21186739","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T09:04:53Z","timestamp":1600074293000},"page":"6739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Sharmeelavathi","family":"Krishnan","sequence":"first","affiliation":[{"name":"Centre of Excellence for Alzheimer\u2019s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasaswi","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Alzheimer\u2019s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7562-4294","authenticated-orcid":false,"given":"Dona P. W.","family":"Jayatunga","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Alzheimer\u2019s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Rea","sequence":"additional","affiliation":[{"name":"Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Health Research Building, Discovery Way, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Martins","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Alzheimer\u2019s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"},{"name":"School of Biomedical Science, Macquarie University, Sydney, NSW 2109, Australia"},{"name":"Alzheimer\u2019s Australia Research Foundation, Nedlands, WA, 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Alzheimer\u2019s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"},{"name":"Alzheimer\u2019s Australia Research Foundation, Nedlands, WA, 6009, Australia"},{"name":"School of Pharmacy and Biomedical Sciences, Curtin Health and Innovation Research Institute (CHIRI), Faculty of Health Sciences, Curtin University, Bentley, WA 6107, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180249","DOI":"10.1098\/rsob.180249","article-title":"Protein damage, ageing and age-related diseases","volume":"9","author":"Krisko","year":"2019","journal-title":"Open Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.cell.2007.10.025","article-title":"An Adaptable Standard for Protein Export from the Endoplasmic Reticulum","volume":"131","author":"Wiseman","year":"2007","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mputhia, Z., Hone, E., Tripathi, T., Sargeant, T.J., Martins, R.N., and Bharadwaj, P. (2019). Autophagy Modulation as a Treatment of Amyloid Diseases. Molecules, 24.","DOI":"10.3390\/molecules24183372"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.jmb.2016.02.004","article-title":"Mechanisms of Selective Autophagy","volume":"428","author":"Zaffagnini","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ncb2979","article-title":"Cargo recognition and trafficking in selective autophagy","volume":"16","author":"Stolz","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_6","first-page":"1304","article-title":"Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer\u2019s disease","volume":"7","author":"Zheng","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s11011-018-0214-6","article-title":"Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases","volume":"33","author":"Pierzynowska","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8452","DOI":"10.1074\/jbc.M306337200","article-title":"Amino Acids and Insulin Control Autophagic Proteolysis through Different Signaling Pathways in Relation to mTOR in Isolated Rat Hepatocytes","volume":"279","author":"Kanazawa","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29900","DOI":"10.1074\/jbc.M003633200","article-title":"Leucine Limitation Induces Autophagy and Activation of Lysosome-dependent Proteolysis in C2C12 Myotubes through a Mammalian Target of Rapamycin-independent Signaling Pathway","volume":"275","author":"Mordier","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.4161\/auto.4240","article-title":"AMP-Activated Protein Kinase: A Universal Regulator of Autophagy?","volume":"3","year":"2007","journal-title":"Autophagy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/ncb1537","article-title":"The energy sensing LKB1\u2013AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis","volume":"9","author":"Liang","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: Process and function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zientara-Rytter, K., and Subramani, S. (2019). The Roles of Ubiquitin-Binding Protein Shuttles in the Degradative Fate of Ubiquitinated Proteins in the Ubiquitin-Proteasome System and Autophagy. Cells, 8.","DOI":"10.3390\/cells8010040"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13041-019-0504-x","article-title":"Autophagic and endo-lysosomal dysfunction in neurodegenerative disease","volume":"12","author":"Malik","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ceb.2010.10.010","article-title":"Protein misfolding disorders and macroautophagy","volume":"23","author":"Menzies","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1093\/hmg\/ddp367","article-title":"Tau fragmentation, aggregation and clearance: The dual role of lysosomal processing","volume":"18","author":"Wang","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/cr.2013.153","article-title":"Chaperone-mediated autophagy: Roles in disease and aging","volume":"24","author":"Cuervo","year":"2013","journal-title":"Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the Pathogenesis of Disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Natural"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","article-title":"Autophagy and the Integrated Stress Response","volume":"40","author":"Kroemer","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1128\/MCB.25.3.1025-1040.2005","article-title":"Inhibition of Macroautophagy Triggers Apoptosis","volume":"25","author":"Boya","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cell.2010.01.028","article-title":"Methods in mammalian autophagy research","volume":"140","author":"Mizushima","year":"2010","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.molcel.2010.10.001","article-title":"Protein Quality Control in the Cytosol and the Endoplasmic Reticulum: Brothers in Arms","volume":"40","author":"Buchberger","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/B978-0-12-407704-1.00005-1","article-title":"Endoplasmic Reticulum and the Unfolded Protein Response","volume":"301","author":"Parra","year":"2013","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.semcdb.2010.04.003","article-title":"Autophagy and innate immunity: Triggering, targeting and tuning","volume":"21","author":"Sumpter","year":"2010","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-Inducible Factors and the Response to Hypoxic Stress","volume":"40","author":"Majmundar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ceb.2009.11.015","article-title":"Hypoxia-induced autophagy: Cell death or cell survival?","volume":"22","author":"Mazure","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/hsz-2012-0119","article-title":"Mitophagy: Mechanisms, pathophysiological roles, and analysis","volume":"393","author":"Ding","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1093\/brain\/awx258","article-title":"PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"140","author":"Du","year":"2017","journal-title":"Brain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1152\/physrev.00013.2006","article-title":"Mitochondrial membrane permeabilization in cell death","volume":"87","author":"Kroemer","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nature04723","article-title":"Loss of autophagy in the central nervous system causes neurodegeneration in mice","volume":"441","author":"Komatsu","year":"2006","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/nature05925","article-title":"Ambra1 regulates autophagy and development of the nervous system","volume":"447","author":"Fimia","year":"2007","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8057","DOI":"10.1523\/JNEUROSCI.2261-06.2006","article-title":"Induction of Autophagy in Axonal Dystrophy and Degeneration","volume":"26","author":"Wang","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.4161\/auto.5.7.9728","article-title":"Targeting autophagy to prevent neonatal stroke damage","volume":"5","author":"Puyal","year":"2009","journal-title":"Autophagy"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1016\/j.bbamcr.2013.06.001","article-title":"Crosstalk between apoptosis, necrosis and autophagy","volume":"1833","author":"Nikoletopoulou","year":"2013","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2005.07.002","article-title":"Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy","volume":"122","author":"Pattingre","year":"2005","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1038\/cddis.2009.16","article-title":"Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria","volume":"1","author":"Wirawan","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1242\/jcs.046250","article-title":"Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis","volume":"122","author":"Betin","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4161\/auto.6.1.10326","article-title":"Control of basal autophagy by calpain1 mediated cleavage of ATG5","volume":"6","author":"Xia","year":"2010","journal-title":"Autophagy"},{"key":"ref_41","first-page":"1124","article-title":"Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis","volume":"8","author":"Yousefi","year":"2006","journal-title":"Natural"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2353\/ajpath.2008.071176","article-title":"Neuronal Apoptosis and Autophagy Cross Talk in Aging PS\/APP Mice, a Model of Alzheimer\u2019s Disease","volume":"173","author":"Yang","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cub.2006.10.053","article-title":"Direct Induction of Autophagy by Atg1 Inhibits Cell Growth and Induces Apoptotic Cell Death","volume":"17","author":"Scott","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.2353\/ajpath.2009.090463","article-title":"Enhancement of Autophagic Flux after Neonatal Cerebral Hypoxia-Ischemia and Its Region-Specific Relationship to Apoptotic Mechanisms","volume":"175","author":"Ginet","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic Levels of p62 Control Cytoplasmic Inclusion Body Formation in Autophagy-Deficient Mice","volume":"131","author":"Komatsu","year":"2007","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2217\/14796708.3.3.309","article-title":"Autophagy in neuroprotection and neurodegeneration: A question of balance","volume":"3","author":"Cherra","year":"2008","journal-title":"Future Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"454","DOI":"10.2353\/ajpath.2008.070876","article-title":"Inhibition of Autophagy Prevents Hippocampal Pyramidal Neuron Death after Hypoxic-Ischemic Injury","volume":"172","author":"Koike","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/sj.cdd.4402231","article-title":"Autophagy is required for necrotic cell death in Caenorhabditis elegans","volume":"15","author":"Samara","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11061","DOI":"10.1074\/jbc.R109.072181","article-title":"Chemical Inducers of Autophagy That Enhance the Clearance of Mutant Proteins in Neurodegenerative Diseases","volume":"285","author":"Renna","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1177\/1073858411404948","article-title":"Neuronal Autophagy as a Mediator of Life and Death","volume":"18","author":"Puyal","year":"2011","journal-title":"Neuroscientist"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1042\/CS20080508","article-title":"Autophagy in disease: A double-edged sword with therapeutic potential","volume":"116","author":"Martinet","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/nrm2529","article-title":"Autophagic cell death: The story of a misnomer","volume":"9","author":"Kroemer","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1006\/mcne.1999.0780","article-title":"Autophagy Is Activated by Apoptotic Signalling in Sympathetic Neurons: An Alternative Mechanism of Death Execution","volume":"14","author":"Xue","year":"1999","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.exger.2005.07.005","article-title":"Protein degradation and aging","volume":"40","author":"Sovak","year":"2005","journal-title":"Exp. Gerontol."},{"key":"ref_55","unstructured":"Segal, H.L., Rothstein, M., and Bergamini, E. (1989). Exploring the age-related changes in hormone-regulated protein breakdown by the use of a physiologic model of stimulation of liver autophagy. Protein Metabolism in Aging, Wiley\u2013Liss."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0531-5565(03)00002-0","article-title":"Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis","volume":"38","author":"Roso","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"B375","DOI":"10.1093\/gerona\/56.9.B375","article-title":"Age-Related Changes in the Autophagic Proteolysis of Rat Isolated Liver Cells: Effects of Antiaging Dietary Restrictions","volume":"56","author":"Donati","year":"2001","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"31505","DOI":"10.1074\/jbc.M002102200","article-title":"Age-related Decline in Chaperone-mediated Autophagy","volume":"275","author":"Cuervo","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-1-4939-2404-2_3","article-title":"Autophagy and Aging","volume":"847","author":"Athonvarangkul","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_60","first-page":"277","article-title":"Autophagy in aging and longevity","volume":"139","author":"Wong","year":"2019","journal-title":"Qual. Life Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Markaki, M., Metaxakis, A., and Tavernarakis, N. (2017). The role of autophagy in aging: Molecular mechanisms. Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Elsevier.","DOI":"10.1016\/B978-0-12-812146-7.00002-0"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pyo, J.-O., Yoo, S.-M., Ahn, H.-H., Nah, J., Hong, S.-H., Kam, T.-I., Jung, S., and Jung, Y.-K. (2013). Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat. Commun., 4.","DOI":"10.1038\/ncomms3300"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/nm.1851","article-title":"Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function","volume":"14","author":"Zhang","year":"2008","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0047-6374(88)90001-2","article-title":"Decline in protease activities with age in the nematode caenorhabditis elegans","volume":"45","author":"Sarkis","year":"1988","journal-title":"Mech. Ageing Dev."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Minnerly, J., Zhang, J., Parker, T., Kaul, T., and Jia, K. (2017). The cell non-autonomous function of ATG-18 is essential for neuroendocrine regulation of Caenorhabditis elegans lifespan. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006764"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.exger.2003.10.019","article-title":"Genetic mouse models of extended lifespan","volume":"38","author":"Liang","year":"2003","journal-title":"Exp. Gerontol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2011.07.030","article-title":"Autophagy and Aging","volume":"146","author":"Rubinsztein","year":"2011","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1089\/rej.2014.1607","article-title":"Can Enhanced Autophagy Be Associated with Human Longevity? Serum Levels of the Autophagy Biomarker Beclin-1 Are Increased in Healthy Centenarians","volume":"17","author":"Emanuele","year":"2014","journal-title":"Rejuvenation Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/ncb1975","article-title":"Induction of autophagy by spermidine promotes longevity","volume":"11","author":"Eisenberg","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1038\/nn.3512","article-title":"Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner","volume":"16","author":"Gupta","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gupta, V.K., Pech, U., Bhukel, A., Fulterer, A., Ender, A., Mauermann, S.F., Andlauer, T.F., Antwi-Adjei, E., Beuschel, C.B., and Thriene, K. (2016). Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. PLoS Biol., 14.","DOI":"10.1371\/journal.pbio.1002563"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.tins.2004.07.005","article-title":"Free radicals and aging","volume":"27","author":"Barja","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Nassif, M., Woehlbier, U., and Manque, P.A. (2017). The delicate balance of autophagy in neurodegeneration. Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Elsevier.","DOI":"10.1016\/B978-0-12-812146-7.00019-6"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10571-016-0386-8","article-title":"Autophagy and Alzheimer\u2019s Disease","volume":"37","author":"Li","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.arr.2011.09.001","article-title":"Morphological and biochemical studies on aging and autophagy","volume":"11","author":"Rezzani","year":"2012","journal-title":"Ageing Res. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1074\/jbc.M506646200","article-title":"Reactivity of Apolipoprotein E4 and Amyloid \u03b2 Peptide","volume":"281","author":"Ji","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nm.3232","article-title":"The role of autophagy in neurodegenerative disease","volume":"19","author":"Nixon","year":"2013","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fendo.2018.00790","article-title":"Hallmarks of Aging: An Autophagic Perspective","volume":"9","author":"Barbosa","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mcn.2015.01.002","article-title":"Autophagy receptor defects and ALS-FTLD","volume":"66","author":"Majcher","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2005.e15","DOI":"10.1016\/j.neurobiolaging.2015.02.014","article-title":"Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: A European early-onset dementia consortium study","volume":"36","author":"Cuyvers","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"245.e1","DOI":"10.1016\/j.neurobiolaging.2017.10.012","article-title":"Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort","volume":"62","author":"Verheijen","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3233\/JAD-180482","article-title":"Next Generation Sequencing Analysis in Early Onset Dementia Patients","volume":"67","author":"Bonvicini","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zou, F., Chai, H.S., Younkin, C.S., Allen, M., Crook, J., Pankratz, V.S., Carrasquillo, M.M., Rowley, C.N., Nair, A.A., and Middha, S. (2012). Brain Expression Genome-Wide Association Study (eGWAS) Identifies Human Disease-Associated Variants. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002707"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.conb.2019.11.024","article-title":"Genetics of Alzheimer\u2019s disease: Where we are, and where we are going","volume":"61","author":"Bellenguez","year":"2020","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.neuron.2018.01.031","article-title":"TREM2 Is a Receptor for \u03b2-Amyloid that Mediates Microglial Function","volume":"97","author":"Zhao","year":"2018","journal-title":"Neuron"},{"key":"ref_86","first-page":"33","article-title":"Sesamin induces autophagy in colon cancer cells by reducing tyrosine phosphorylation of EphA1 and EphB2","volume":"39","author":"Watanabe","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"F160","DOI":"10.1152\/ajprenal.00304.2015","article-title":"Requirement of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells","volume":"310","author":"Alnasser","year":"2016","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1038\/ncomms6775","article-title":"Clusterin facilitates stress-induced lipidation of LC3 and autophagosome biogenesis to enhance cancer cell survival","volume":"5","author":"Zhang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4998","DOI":"10.1038\/ncomms5998","article-title":"PICALM modulates autophagy activity and tau accumulation","volume":"5","author":"Moreau","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/nature12313","article-title":"The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy","volume":"500","author":"Heldring","year":"2013","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e792","DOI":"10.1038\/cddis.2013.308","article-title":"WWOX suppresses autophagy for inducing apoptosis in methotrexate-treated human squamous cell carcinoma","volume":"4","author":"Tsai","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/15548627.2019.1633862","article-title":"MAPT\/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-III complex formation: A vicious cycle in Alzheimer neurodegeneration","volume":"16","author":"Feng","year":"2019","journal-title":"Autophagy"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-017-0077-5","article-title":"Protein misfolding in neurodegenerative diseases: Implications and strategies","volume":"6","author":"Sweeney","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3109\/10408360903335821","article-title":"The structure and function of Alzheimer\u2019s gamma secretase enzyme complex","volume":"46","author":"Krishnaswamy","year":"2009","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-0173(03)00174-7","article-title":"Amyloid-\u03b2: A chameleon walking in two worlds: A review of the trophic and toxic properties of amyloid-\u03b2","volume":"43","author":"Atwood","year":"2003","journal-title":"Brain Res. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1582-4934.2009.00609.x","article-title":"A\u03b2 aggregation and possible implications in Alzheimer\u2019s disease pathogenesis","volume":"13","author":"Bharadwaj","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.tibs.2015.10.002","article-title":"Amyloid Fibres: Inert End-Stage Aggregates or Key Players in Disease?","volume":"40","author":"Tipping","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"105020","DOI":"10.1016\/j.nbd.2020.105020","article-title":"Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer\u2019s disease brain","volume":"143","author":"Lau","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Haghi, M., Masoudi, R., and Najibi, S.M. (2020). Distinctive alteration in the expression of autophagy genes in Drosophila models of amyloidopathy and tauopathy. Upsala J. Med Sci., 1\u20139.","DOI":"10.1080\/03009734.2020.1785063"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.arr.2017.09.005","article-title":"Autophagy, its mechanisms and regulation: Implications in neurodegenerative diseases","volume":"40","author":"Moloudizargari","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4161\/auto.1.1.1513","article-title":"Autophagy and its possible roles in nervous system diseases, damage and repair","volume":"1","author":"Rubinsztein","year":"2005","journal-title":"Autophagy"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nrd2272","article-title":"Potential therapeutic applications of autophagy","volume":"6","author":"Rubinsztein","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Williams, A., Jahreiss, L., Sarkar, S., Saiki, S., Menzies, F., Ravikumar, B., and Rubinsztein, D. (2006). Aggregate-prone proteins are cleared from the cytosol by autophagy: Therapeutic implications. Curr. Top. Dev. Biol., 89\u2013101.","DOI":"10.1016\/S0070-2153(06)76003-3"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/S1474-4422(07)70076-5","article-title":"Autophagy and neurodegeneration: When the cleaning crew goes on strike","volume":"6","author":"Cuervo","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1126\/science.1099993","article-title":"Autophagy in Health and Disease: A Double-Edged Sword","volume":"306","author":"Shintani","year":"2004","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41419-019-1464-x","article-title":"Neuronal AMP-activated protein kinase hyper-activation induces synaptic loss by an autophagy-mediated process","volume":"10","author":"Domise","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"476","DOI":"10.4161\/auto.5719","article-title":"SNF4A\u03b3, the Drosophila AMPK \u03b3 subunit is required for regulation of developmental and stress-induced autophagy","volume":"4","author":"Lippai","year":"2008","journal-title":"Autophagy"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6926","DOI":"10.1523\/JNEUROSCI.0800-08.2008","article-title":"Autophagy Induction and Autophagosome Clearance in Neurons: Relationship to Autophagic Pathology in Alzheimer\u2019s Disease","volume":"28","author":"Boland","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3233\/JAD-190948","article-title":"PRKAG2 Gene Expression Is Elevated and its Protein Levels Are Associated with Increased Amyloid-\u03b2 Accumulation in the Alzheimer\u2019s Disease Brain","volume":"74","author":"Bharadwaj","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"103466","DOI":"10.1016\/j.mcn.2020.103466","article-title":"Autophagy modulates A\u03b2 accumulation and formation of aggregates in yeast","volume":"104","author":"Bharadwaj","year":"2020","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1016\/j.biocel.2004.02.005","article-title":"Methods for monitoring autophagy","volume":"36","author":"Mizushima","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/jnen\/64.2.113","article-title":"Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study","volume":"64","author":"Wegiel","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1083\/jcb.200505082","article-title":"Macroautophagy\u2014A novel \u03b2-amyloid peptide-generating pathway activated in Alzheimer\u2019s disease","volume":"171","author":"Yu","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.arr.2016.04.010","article-title":"Lysosomal cathepsins and their regulation in aging and neurodegeneration","volume":"32","author":"Stoka","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1242\/jcs.019265","article-title":"Autophagy, amyloidogenesis and Alzheimer disease","volume":"120","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1016\/j.biocel.2004.05.010","article-title":"Autophagic vacuoles are enriched in amyloid precursor protein-secretase activities: Implications for \u03b2-amyloid peptide over-production and localization in Alzheimer\u2019s disease","volume":"36","author":"Yu","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_117","first-page":"2190","article-title":"The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid \u03b2 accumulation in mice","volume":"118","author":"Pickford","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7218","DOI":"10.1523\/JNEUROSCI.2574-18.2019","article-title":"Neuroinflammation and Functional Connectivity in Alzheimer\u2019s Disease: Interactive Influences on Cognitive Performance","volume":"39","author":"Passamonti","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.bcp.2014.01.008","article-title":"Microglial dysfunction in brain aging and Alzheimer\u2019s disease","volume":"88","author":"Mosher","year":"2014","journal-title":"Biochem. Pharm."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1042\/BST20140107","article-title":"Glia in the pathogenesis of neurodegenerative diseases","volume":"42","author":"Verkhratsky","year":"2014","journal-title":"Biochem. Soc. Trans."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1523\/JNEUROSCI.5572-08.2009","article-title":"Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis","volume":"29","author":"Mandrekar","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/glia.20599","article-title":"Transplanted astrocytes internalize deposited \u03b2-amyloid peptides in a transgenic mouse model of Alzheimer\u2019s disease","volume":"56","author":"Pihlaja","year":"2007","journal-title":"Glia"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1038\/cddis.2009.2","article-title":"Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer\u2019s disease","volume":"1","author":"Rodriguez","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_124","first-page":"1","article-title":"A\u03b2 Internalization by Neurons and Glia","volume":"2011","author":"Mohamed","year":"2011","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Wright, A.L., Zinn, R., Hohensinn, B., Konen, L.M., Beynon, S.B., Tan, R.P., Clark, I.A., Abdipranoto, A., and Vissel, B. (2013). Neuroinflammation and Neuronal Loss Precede A\u03b2 Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer\u2019s Disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059586"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/hipo.22503","article-title":"Glial alterations from early to late stages in a model of Alzheimer\u2019s disease: Evidence of autophagy involvement in A\u03b2 internalization","volume":"26","author":"Pomilio","year":"2015","journal-title":"Hippocampus"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature04724","article-title":"Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice","volume":"441","author":"Hara","year":"2006","journal-title":"Nature"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Liu, J., and Li, L. (2019). Targeting Autophagy for the Treatment of Alzheimer\u2019s Disease: Challenges and Opportunities. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00203"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1021\/acschemneuro.9b00317","article-title":"Autophagy Promotes Memory Formation","volume":"10","author":"Tripathi","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/hmg\/ddi458","article-title":"Rapamycin alleviates toxicity of different aggregate-prone proteins","volume":"15","author":"Berger","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/hmg\/11.9.1107","article-title":"Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy","volume":"11","author":"Ravikumar","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ng1362","article-title":"Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease","volume":"36","author":"Ravikumar","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"25009","DOI":"10.1074\/jbc.M300227200","article-title":"\u03b1-Synuclein Is Degraded by Both Autophagy and the Proteasome","volume":"278","author":"Webb","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd.2018.109","article-title":"Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing","volume":"17","author":"Boland","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Chen, X., Dong, G., and Wang, L. (2020). High-frequency transcranial magnetic stimulation protects APP\/PS1 mice against Alzheimer\u2019s disease progress by reducing APOE and enhancing autophagy. Brain Behav., 10.","DOI":"10.1002\/brb3.1740"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"mTOR: A pharmacologic target for autophagy regulation","volume":"125","author":"Kim","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"12396","DOI":"10.1523\/JNEUROSCI.6189-11.2012","article-title":"Rapamycin delays disease onset and prevents prp plaque deposition in a mouse model of gerstmann-straussler-scheinker disease","volume":"32","author":"Cortes","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2014.05.032","article-title":"Temsirolimus attenuates tauopathy in vitro and in vivo by targeting tau hyperphosphorylation and autophagic clearance","volume":"85","author":"Jiang","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Ozcelik, S., Fraser, G., Castets, P., Schaeffer, V., Skachokova, Z., Breu, K., Clavaguera, F., Sinnreich, M., Kappos, L., and Goedert, M. (2013). Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062459"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Spilman, P., Podlutskaya, N., Hart, M.J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., and Galvan, V. (2010). Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-\u03b2 Levels in a Mouse Model of Alzheimer\u2019s Disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009979"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1172\/JCI44145","article-title":"Next-generationmTOR inhibitors in clinical oncology: How pathway complexity informs thera-peutic strategy","volume":"121","author":"Wander","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"ra21","DOI":"10.1126\/scisignal.aac5472","article-title":"Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis","volume":"9","author":"DeBosch","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.bbrc.2015.08.076","article-title":"Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease","volume":"465","author":"Tanji","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3858\/emm.2012.44.2.031","article-title":"Neuronal autophagy and neurodegenerative diseases","volume":"44","author":"Son","year":"2012","journal-title":"Exp. Mol. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/mp.2012.106","article-title":"Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer\u2019s mouse model","volume":"18","author":"Steele","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e332","DOI":"10.1038\/tp.2013.97","article-title":"Latrepirdine: Molecular mechanisms underlying potential therapeutic roles in Alzheimer\u2019s and other neurodegenerative diseases","volume":"3","author":"Bharadwaj","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Bharadwaj, P., and Martins, R. (2019). A rapid absorbance-based growth assay to screen oligomer A\u03b2 toxicity and protection against cell death in yeast. Neural Regen. Res., accepted.","DOI":"10.4103\/1673-5374.280318"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3233\/JAD-2012-120178","article-title":"Latrepirdine (Dimebon\u2122) enhances autophagy and reduces intracellular GFP-A\u03b242 levels in yeast","volume":"32","author":"Bharadwaj","year":"2012","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_149","unstructured":"Ntsapi, C., Swart, C., Lumkwana, D., and Loos, B. (2012). Autophagic flux failure in neurodegeneration: Identifying the defect and compensating flux offset. Autophagy Current Trends Cell. Physiol. Pathol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"15120","DOI":"10.1073\/pnas.1606899113","article-title":"Loss ofO-GlcNAc glycosylation in forebrain excitatory neurons induces neurodegeneration","volume":"113","author":"Wang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6739\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:09:51Z","timestamp":1760177391000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,14]]},"references-count":151,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21186739"],"URL":"https:\/\/doi.org\/10.3390\/ijms21186739","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,14]]}}}