Paper

The Role of Autophagy in Age-Related Neurodegeneration
Brett A. McCray, J. Paul Taylor

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA

Address of Corresponding Author

Neurosignals 2008;16:75-84 (DOI: 10.1159/000109761)

  Key Words

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

  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.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

J. Paul Taylor
Taylor Lab, 233 Stemmler Hall
3450 Hamilton Walk
Philadelphia, PA 19104 (USA)
Tel. +1 215 573 2270, Fax +1 215 573 1153, E-Mail jpt@mail.med.upenn.edu

  Article Information

Published online: December 5, 2007
Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 0, Number of References : 76