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 journalArticle

37 Citations (Scopus)

Abstract

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
Article number64284
Pages (from-to)2517-2524
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

Fingerprint

Autophagy
Amyotrophic Lateral Sclerosis
Ubiquitinated Proteins
Motor Neurons
Lysosomes
Neurodegenerative Diseases
Organelles
Cytoplasm
Homeostasis
Mutation
Membranes
Enzymes
Genes
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis. / Lee, Jae Keun; Shin, Jin Hee; Lee, Ji Eun; Choi, Eui Ju.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1852, No. 11, 64284, 01.11.2015, p. 2517-2524.

Research output: Contribution to journalArticle

@article{b4be0f40e0174187a5921a4162f1d9b5,
title = "Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis",
abstract = "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.",
keywords = "Amyotrophic lateral sclerosis, Autophagosome, Autophagy, Lysosome, Neurodegeneration",
author = "Lee, {Jae Keun} and Shin, {Jin Hee} and Lee, {Ji Eun} and Choi, {Eui Ju}",
year = "2015",
month = "11",
day = "1",
doi = "10.1016/j.bbadis.2015.08.005",
language = "English",
volume = "1852",
pages = "2517--2524",
journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "11",

}

TY - JOUR

T1 - Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis

AU - Lee, Jae Keun

AU - Shin, Jin Hee

AU - Lee, Ji Eun

AU - Choi, Eui Ju

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - Amyotrophic lateral sclerosis

KW - Autophagosome

KW - Autophagy

KW - Lysosome

KW - Neurodegeneration

UR - http://www.scopus.com/inward/record.url?scp=84941247779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941247779&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2015.08.005

DO - 10.1016/j.bbadis.2015.08.005

M3 - Article

AN - SCOPUS:84941247779

VL - 1852

SP - 2517

EP - 2524

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 11

M1 - 64284

ER -