Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Review

Lee, Jae Keun¹  Shin, Jin Hee²  Lee, Ji Eun^3,4  Choi, Eui-Ju¹ 

[1] Korea Univ, Dept Life Sci, Lab Cell Death & Human Dis, Seoul, South Korea

[2] Ajou Univ, Sch Med, Dept Microbiol, Suwon 443749, South Korea

[3] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul, South Korea

[4] Samsung Med Ctr, SGI, Seoul 135710, South Korea

关键词: Amyotrophic lateral sclerosis;    Autophagosome;    Autophagy;    Lysosome;    Neurodegeneration;   

DOI  :  10.1016/j.bbadis.2015.08.005

来源: Elsevier

【 摘 要 】

Amyotrophic lateral sclerosis (ALE) is a late-onset neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons associated with the abnormal aggregation of ubiquitinated proteins. The molecular mechanisms underlying the pathogenesis of ALS remain unclear, however. Autophagy is a major pathway for the elimination of protein aggregates and damaged organelles and therefore contributes to cellular homeostasis. This catabolic process begins with the formation of the double membrane-bound autophagosome that engulfs portions of the cytoplasm and subsequently fuses with a lysosome to form an autolysosome, in which lysosomal enzymes digest autophagic substrates. Defects at various stages of autophagy have been associated with pathological mutations of several ALE-linked genes including SOD1, p62, TDP-43, and optineurin, suggesting that such defects may play a causative role in the pathogenesis of this condition. In this review, we summarize the dysregulation of autophagy associated with ALE as well as potential therapeutic strategies based on modulation of the autophagic process. (C) 2015 Elsevier B.V. All rights reserved.

【 授权许可】

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