The role of autophagy in age-related neurodegeneration

Brett A. McCray, J. Paul Taylor

Research output: Contribution to journalReview articlepeer-review

Abstract

Most age-related neurodegenerative diseases are characterized by accumulation of aberrant protein aggregates in affected brain regions. In many cases, these proteinaceous deposits are composed of ubiquitin conjugates, suggesting a failure in the clearance of proteins targeted for degradation. The 2 principal routes of intracellular protein catabolism are the ubiquitin proteasome system and the autophagy-lysosome system (autophagy). Both of these degradation pathways have been implicated as playing important roles in the pathogenesis of neurodegenerative disease. Here we describe autophagy and review the evidence suggesting that impairment of autophagy contributes to the initiation or progression of age-related neurodegeneration. We also review recent evidence indicating that autophagy may be exploited to remove toxic protein species, suggesting novel strategies for therapeutic intervention for a class of diseases for which no effective treatments presently exist.

Original languageEnglish (US)
Pages (from-to)75-84
Number of pages10
JournalNeuroSignals
Volume16
Issue number1
DOIs
StatePublished - Dec 2007
Externally publishedYes

Keywords

  • Aging
  • Autophagy
  • Lysosome
  • Neurodegeneration
  • Protein aggregation
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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