Overview:

SIRT2 is a member of the sirtuin family of proteins which are homologs to the yeast Sir2 protein. Sirtuin family contain a sirtuin core domain and are grouped into four classes with SIRT2 being a member of class I. Inhibition of SIRT2 can lead to neuroprotection in cellular and invertebrate models of Huntington's disease (1). Huntington's disease is characterized by increased sterol synthesis in neuronal cells and this process is reversed by SIRT2 inhibition. SIRT2 can deacetylate lys40 of alpha-tubulin both in vitro and in vivo (2). Knockdown of SIRT2 via small interfering RNA results in tubulin hyperacetylation.

References:

1. Luthi-Carter, R. Et al: SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.2. North, B. J. et al: The human Sir2 ortholog, SIRT2, is an NAD(+)-dependent tubulin deacetylase. Molec. Cell 11: 437-444, 2003.