The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington's Disease Mouse Models

Vanita Chopra, Luisa Quinti, Jinho Kim, Lorraine Vollor, K. Lakshmi Narayanan, Christina Edgerly, Patricia M. Cipicchio, Molly A. Lauver, Soo Hyuk Choi, Richard B. Silverman, Robert J. Ferrante, Steven Hersch, Aleksey G. Kazantsev

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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.

Original languageEnglish
Pages (from-to)1492-1497
Number of pages6
JournalCell Reports
Volume2
Issue number6
DOIs
Publication statusPublished - 2012 Dec 27

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chopra, V., Quinti, L., Kim, J., Vollor, L., Narayanan, K. L., Edgerly, C., Cipicchio, P. M., Lauver, M. A., Choi, S. H., Silverman, R. B., Ferrante, R. J., Hersch, S., & Kazantsev, A. G. (2012). The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington's Disease Mouse Models. Cell Reports, 2(6), 1492-1497. https://doi.org/10.1016/j.celrep.2012.11.001