SIRT1 Protects against α-Synuclein Aggregation by Activating Molecular Chaperones
Author(s)Donmez Yalcin, Gizem; Arun, Anirudh; Chung, Chee Yeun; McLean, Pamela J.; Lindquist, Susan; Guarente, Leonard Pershing; ... Show more Show less
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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.
DepartmentMassachusetts 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)
Journal of Neuroscience
Society for Neuroscience
Donmez, G. et al. “SIRT1 Protects Against -Synuclein Aggregation by Activating Molecular Chaperones.” Journal of Neuroscience 32.1 (2012): 124–132.
Final published version