Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice - PubMed (original) (raw)
. 2006 Jun 15;441(7095):885-9.
doi: 10.1038/nature04724. Epub 2006 Apr 19.
Affiliations
- PMID: 16625204
- DOI: 10.1038/nature04724
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Taichi Hara et al. Nature. 2006.
Abstract
Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.
Comment in
- Neurodegeneration: good riddance to bad rubbish.
Klionsky DJ. Klionsky DJ. Nature. 2006 Jun 15;441(7095):819-20. doi: 10.1038/441819a. Nature. 2006. PMID: 16778876 No abstract available. - The importance of 'self-eating'.
Wrighton KH. Wrighton KH. Nat Rev Mol Cell Biol. 2010 Oct;11(10):681. doi: 10.1038/nrm2978. Nat Rev Mol Cell Biol. 2010. PMID: 20861878 No abstract available.
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