The sirtuin SIRT2 is a deacetylase which targets α-tubulin, histone 4, forkhead transcription factors, and several other substrates. It has roles in metabolic diseases, cancer, age-related disorders, and neurodegenerative diseases, potentially including Alzheimer’s, Huntington’s, and Parkinson’s diseases. AK-7 is a cell- and brain-permeable inhibitor of SIRT2 (IC50 = 15.5 μM). In culture, it dimishes neuronal cell death induced by mutant huntingtin fragment. In addition, AK-7 down-regulates cholesterol biosynthetic gene expression and reduces total cholesterol levels in neurons in vivo.
