Autophagy for the avoidance of neurodegeneration.
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.
Madeo
Frank
F
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria. frank.madeo@uni-graz.at
Eisenberg
Tobias
T
Kroemer
Guido
G
D000375:Aging / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D000071701:Regulatory Factor X Transcription Factors; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; C000606290:SOD1 protein, human; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1