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Regulatory enzyme overexpression may protect against neurodegeneration in Huntington's disease
Date:12/18/2011

Treatment that increases brain levels of an important regulatory enzyme may slow the loss of brain cells that characterizes Huntington's disease (HD) and other neurodegenerative disorders. In a report receiving advance online publication in Nature Medicine, a Massachusetts General Hospital (MGH)-based research team reports that increased expression of Sirt1, one of a family of enzymes called sirtuins, in the brain of a mouse model of HD protected against neurodegeneration. They also identified a potential mechanism for this protective effect.

"Diseases such as Huntington's, Parkinson's and Alzheimer's disease have different causative factors, but they share common themes such as aggregation of misfolded proteins and a unifying endpoint, the degenerative loss of neurons," says Dimitri Krainc, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), the study's senior author. "Pharmacological targeting of Sirt1 may provide an opportunity for therapeutic development in HD and, more generally, in the neurodegenerative disorders of aging."

HD is an inherited disorder caused by a mutation in the gene for a protein called huntingtin. Deposits of the abnormal protein accumulate within the brain, causing destruction of brain cells. Symptoms of HD usually first appear in the middle years and worsen over the 10- to 30-year course of the disorder, leading to death from a variety of complications. Sirt1 is an important regulator of the activity of proteins involved in many critical functions including energy metabolism, inflammation and stress tolerance and recent studies have suggested it protects against the effects of several neurodegenerative diseases.

In experiments with a mouse model of HD, the researchers first showed that knocking out Sirt1 expression in the brain accelerated the appearance of HD-like pathology such as aggregates of mutant huntingtin and increased cell damage in key areas of the
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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