A Therapeutic Target for Inhibition of Neurodegeneration: Autophagy

• Published in: Zurnal vyss̆ej nervnoj dejatelnosti imeni I P Pavlova Vol. 66; no. 5; p. 515
• Main Authors: Pupyshev, A B, Korolenko, T A, Tikhonova, M A
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01-09-2016
• Subjects: alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Animals; Autophagy - drug effects; Autophagy - genetics; Clinical Trials as Topic; Gene Expression Regulation; Humans; Huntingtin Protein - genetics; Huntingtin Protein - metabolism; Huntington Disease - drug therapy; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Metformin - therapeutic use; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Molecular Targeted Therapy - methods; Neuroprotective Agents - therapeutic use; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; Sirolimus - therapeutic use; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Ubiquitin - genetics; Ubiquitin - metabolism
• ISSN: 0044-4677
• DOI: 10.7868/S0044467716050087

The role of autophagy in cell survival and suppression of neurodegeneration was considered. We discussed its involvement in Alzheimer's, Parkinson's, and Huntington's diseases connected with accumulation of amy- loid-β, α-synuclein, and huntingtin, respectively. Autophagy is reduced in these diseases and in aging as well to various extent. Elimination of accumulated toxic proteins and structures is performed by autophagy mech- anisms (chaperon-mediated autophagy, macroautophagy, selected autophagy) in an interaction with ubiqui- tin-proteasome system. In many cases activation of mTOR-dependent autophagy and mTOR-independent regulatory pathways lead to the therapeutic effect of inhibition of neurodegeneration in cell cultures and an- imal models. Some autophagy enhancers such as resveratrol, metformin, rilmenidine, lithium, and curcumin are tested now in clinical trials.