Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis

Jae Keun Lee, Jin Hee Shin, Ji Eun Lee, Eui Ju Choi

Research output: Contribution to journalReview articlepeer-review

70 Citations (Scopus)


Amyotrophic lateral sclerosis (ALS) 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 ALS-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 ALS as well as potential therapeutic strategies based on modulation of the autophagic process.

Original languageEnglish
Pages (from-to)2517-2524
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number11
Publication statusPublished - 2015 Nov 1

Bibliographical note

Funding Information:
The work in the authors' laboratories was supported by the National Research Foundation grants ( 2006–0093855 , 2009–0080985 to E.-J.C., 2013R1A1A1059056 to J.E.L., 2014R1A1A1002076 to J.K.L., and 2014R1A1A3052540 to J.H.S.) funded by the Ministry of Science, ICT, and Future Planning of Korea, by Korea University grants (to E.-J.C. and to J.K.L), and by a grant from the Samsung Medical Center ( GFO1150121 to J.E.L.).

Publisher Copyright:
© 2015 Elsevier B.V.


  • Amyotrophic lateral sclerosis
  • Autophagosome
  • Autophagy
  • Lysosome
  • Neurodegeneration

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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