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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Comment
MeSH terms
-
Aging / physiology
-
Amyotrophic Lateral Sclerosis / physiopathology*
-
Animals
-
Autophagy / genetics
-
Autophagy / physiology*
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / metabolism
-
Gene Knockout Techniques
-
Homeostasis / physiology
-
Humans
-
Neurons / pathology
-
Neurons / physiology*
-
Regulatory Factor X Transcription Factors
-
Superoxide Dismutase / metabolism
-
Superoxide Dismutase-1
-
Transcription Factors / genetics*
-
Transcription Factors / metabolism
-
X-Box Binding Protein 1
Substances
-
DNA-Binding Proteins
-
Regulatory Factor X Transcription Factors
-
SOD1 protein, human
-
Transcription Factors
-
X-Box Binding Protein 1
-
XBP1 protein, human
-
Superoxide Dismutase
-
Superoxide Dismutase-1