Novel SIRT2 inhibitor protects against neuronal damage in animal models of Huntington's

Published on November 30, 2012 at 1:12 AM · No Comments

Treatment with a novel agent that inhibits the activity of SIRT2, an enzyme that regulates many important cellular functions, reduced neurological damage, slowed the loss of motor function and extended survival in two animal models of Huntington's disease. The study led by Massachusetts General Hospital (MGH) researchers will appear in the Dec. 27 issue of Cell Reports and is receiving advance online release.

"I believe that the drug efficacy demonstrated in two distinct genetic HD mouse models is quite unique and highly encouraging," says Aleksey Kazantsev, PhD, of the MassGeneral Institute for Neurodegenerative Disorders, senior author of the study. "The outcome suggests that designing stronger SIRT2 inhibitors is a valid strategy for developing drugs to slow the progression of HD, something that currently does not exist."

Earlier studies by Kazantsev's group and others showed that inhibiting SIRT2 (sirtuin-2 deacetylase) protected against neuronal damage in cellular and animal models of HD and Parkinson's disease - both of which are characterized by the buildup of abnormal proteins in the brain - and in other neurodegenerative disorders. The current study was designed to evaluate in two mouse models of HD use of a new, brain-permeable SIRT2 inhibitor called AK-7, first identified by members of the MGH team in 2011. One model called R6/2 is characterized by robust progression and severity of neurological symptoms. The other, called 140 CAG Htt knock-in, is genetically closer to the human disease. In both models, the mutated huntingtin gene contains extended repeats of the nucleotide triplet CAG, leading to development of HD-like motor symptoms and the same type of brain damage seen in the devastating neurological disorder.

Read in | English | Español | Français | Deutsch | Português | Italiano | 日本語 | 한국어 | 简体中文 | 繁體中文 | Nederlands | Русский | Svenska | Polski
Comments
The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
Post a new comment
Post