SIRT1 Protects against α-Synuclein Aggregation by Activating Molecular Chaperones
Name
Donmez-2012-SIRT1 Protects again.pdf
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Author(s)
Donmez Yalcin, Gizem
Arun, Anirudh
Chung, Chee Yeun
McLean, Pamela J.
Lindquist, Susan
Guarente, Leonard Pershing
Date Issued
May 2012
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Donmez, G. et al. “SIRT1 Protects Against -Synuclein Aggregation by Activating Molecular Chaperones.” Journal of Neuroscience 32.1 (2012): 124–132.
Version
Final published version
Abstract
α-Synuclein is a key molecule in the pathogenesis of synucleinopathy including dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. Sirtuins are NAD[superscript +]-dependent protein deacetylases that are highly conserved and counter aging in lower organisms. We show that the life span of a mouse model with A53T α-synuclein mutation is increased by overexpressing SIRT1 and decreased by knocking out SIRT1 in brain. Furthermore, α-synuclein aggregates are reduced in the brains of mice with SIRT1 overexpression and increased by SIRT1 deletion. We show that SIRT1 deacetylates HSF1 (heat shock factor 1) and increases HSP70 RNA and protein levels, but only in the brains of mice with A53T and SIRT1 expression. Thus, SIRT1 responds to α-synuclein aggregation-induced stress by activating molecular chaperones to protect against disease.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1523/jneurosci.3442-11.2012
