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The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models.

ABSTRACT: Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans.

SUBMITTER: Chopra V

PROVIDER: S-EPMC3534897 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models.

Chopra Vanita V Quinti Luisa L Kim Jinho J Vollor Lorraine L Narayanan K Lakshmi KL Edgerly Christina C Cipicchio Patricia M PM Lauver Molly A MA Choi Soo Hyuk SH Silverman Richard B RB Ferrante Robert J RJ Hersch Steven S Kazantsev Aleksey G AG

Cell reports 20121129 6

Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical ...[more]

PMID: 23200855

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