Autophagy for the avoidance of neurodegeneration
- 1Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria;
- 2INSERM, U848; 94805 Villejuif, France;
- 3Institut Gustave Roussy, 94805 Villejuif, France;
- 4University Paris Sud, Paris-11, 94805 Villejuif, France
Abstract
Cellular defense mechanisms, including the unfolded protein response (UPR) and autophagy, attempt to resolve toxic protein aggregates, which are common denominators of neurodegenerative diseases. In this issue of Genes & Development, Hetz and colleagues (pp. 2294–2306) surprisingly show that inhibition of the UPR by knockout of XBP-1 causes a massive increase in autophagy, enhances clearance of superoxide dismutase 1 (SOD1) aggregates, and delays the development of amyotrophic lateral sclerosis. These findings suggest the existence of a homeostatic—if not hormetic—balance between distinct cellular defense mechanisms.
Keywords
- Amyotrophic lateral sclerosis
- unfolded protein response
- endoplasmic reticulum stress
- XBP-1
- autophagy
Footnotes
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↵5 Corresponding authors.
E-MAIL frank.madeo{at}uni-graz.at; FAX 43-316-3809898.
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↵6 E-MAIL kroemer{at}orange.fr; FAX 33-1-42-11-60-47.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1858009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
