The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia

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The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia

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Title: The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia
Author: Chen, Xiqun; Wales, Pauline; Quinti, Luisa; Zuo, Fuxing; Moniot, Sébastien; Herisson, Fanny; Rauf, Nazifa Abdul; Wang, Hua; Silverman, Richard B.; Ayata, Cenk; Maxwell, Michelle M.; Steegborn, Clemens; Schwarzschild, Michael A.; Outeiro, Tiago F.; Kazantsev, Aleksey G.

Note: Order does not necessarily reflect citation order of authors.

Citation: Chen, X., P. Wales, L. Quinti, F. Zuo, S. Moniot, F. Herisson, N. A. Rauf, et al. 2015. “The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia.” PLoS ONE 10 (1): e0116919. doi:10.1371/journal.pone.0116919. http://dx.doi.org/10.1371/journal.pone.0116919.
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Abstract: Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson’s disease, amyotrophic lateral sclerosis and cerebral ischemia. Our results demonstrate that AK7 is neuroprotective in models of Parkinson’s disease; it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic neuron loss in vivo. The compound does not show beneficial effects in mouse models of amyotrophic lateral sclerosis and cerebral ischemia. These findings underscore the specificity of protective effects observed here in models of Parkinson’s disease, and previously in Huntington’s disease, and support the development of SIRT2 inhibitors as potential therapeutics for the two neurodegenerative diseases.
Published Version: doi:10.1371/journal.pone.0116919
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301865/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890732
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