Exp Mol Med.  2012 Feb;44(2):89-98. 10.3858/emm.2012.44.2.031.

Neuronal autophagy and neurodegenerative diseases

Affiliations
  • 1Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 120-750, Korea. hjson@ewha.ac.kr
  • 2Division of Life and Pharmaceutical Sciences, College of Pharmacy, Brain Disease Research Institute, Ewha Womans University, Seoul 120-750, Korea.

Abstract

Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.

Keyword

Alzheimer disease; amyotrophic lateral sclerosis; autophagy; Huntington disease; neurodegenerative diseases; neurons; Parkinson disease

MeSH Terms

Alzheimer Disease/metabolism/pathology/physiopathology
Animals
Autophagy/*physiology
Humans
Huntington Disease/metabolism/pathology/physiopathology
Models, Biological
Neurodegenerative Diseases/metabolism/*pathology/physiopathology
Neurons/*cytology
Parkinson Disease/metabolism/pathology/physiopathology
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