Pharmacological Tools to Modulate Autophagy in Neurodegenerative Diseases

被引:28
作者
Suresh, S. N. [3 ]
Chakravorty, Anushka [1 ]
Giridharan, Mridhula [1 ]
Garimella, Lakshmi [1 ]
Manjithaya, Ravi [1 ,2 ]
机构
[1] Jawaharlal Nehru Ctr Adv Sci Res, Mol Biol & Genet Unit, Autophagy Lab, Bangalore 560064, Karnataka, India
[2] Jawaharlal Nehru Ctr Adv Sci Res, Neurosci Unit, Bangalore 560064, Karnataka, India
[3] Indian Inst Sci, Ctr Brain Res, Bangalore 560012, Karnataka, India
基金
英国惠康基金;
关键词
Autophagy modulators; Aggrephagy; Misfolded proteins; Neuroprotection; Aggresome; AMYOTROPHIC-LATERAL-SCLEROSIS; CHAPERONE-MEDIATED AUTOPHAGY; UBIQUITIN-PROTEASOME PATHWAY; POTENTIAL THERAPEUTIC TARGET; CYCLIN-DEPENDENT KINASE-5; ACTIVATED PROTEIN-KINASE; GENOME-WIDE ASSOCIATION; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; MOUSE MODEL;
D O I
10.1016/j.jmb.2020.02.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Considerable evidences suggest a link between autophagy dysfunction, protein aggregation, and neurodegenerative diseases. Given that autophagy is a conserved intracellular housekeeping process, modulation of autophagy flux in various model organisms have highlighted its importance for maintaining proteostasis. In postmitotic cells such as neurons, compromised autophagy is sufficient to cause accumulation of ubiquitinated aggregates, neuronal dysfunction, degeneration, and loss of motor coordination-all hallmarks of neurodegenerative diseases. Reciprocally, enhanced autophagy flux augments cellular and organismal health, in addition to extending life span. These genetic studies not-withstanding a plethora of small molecule modulators of autophagy flux have been reported that alleviate disease symptoms in models of neurodegenerative diseases. This review summarizes the potential of such molecules to be, perhaps, one of the first autophagy drugs for treating these currently incurable diseases. (C) 2020 The Author(s). Published by Elsevier Ltd. This is an open
引用
收藏
页码:2822 / 2842
页数:21
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