Sirt1, in excess, could protect against Huntington's disease

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As an all-purpose "fountain of youth," the family of enzymes known as sirtuins remains controversial. But Sirt1, one of its illustrious members, may have another more specific beneficial use. Scientists believe that overexpressing the enzyme may protect against neurodegeneration caused by Huntington's disease.

It's a wonderful example of "too much of a good thing" potentially being, well, a good thing.

The finding stems from a substantial scientific team led by Massachusetts General Hospital researchers but also including scientists from the Massachusetts Institute of Technology, Scripps Research Institute and the Novartis Institutes for BioMedical Research. Separately, researchers from The Johns Hopkins School of Medicine reported similar news. Both scientific efforts are featured online in Nature Medicine.

Huntington's disease involves a mutation of the gene for the huntingtin protein, which causes abnormal protein deposits in the brain, neurodegeneration and eventually death.

Scientists established their thesis first by showing in mice that stopping the expression of Sirt1 in the brain increased Huntington's symptoms, such as more of the huntingtin mutation and more cell damage. Mice with an overexpression of Sirt1 lived longer, showed smaller amounts of the huntingtin mutation and also developed less neurological damage than their counterparts without the Sirt1 expression. Subsequent expressions showed excess amounts of Sirt1 protected neurons from huntingtin toxicity, the researchers said.

Skeptics have heard the song and dance about sirtuins before, at least as an aging panacea. Still, these experiments, if they can be replicated in people, offer hope for patients with Huntington's and other aging-related neurodegenerative diseases such as Alzheimer's and Parkinson's, the researchers argue.

Potential Sirt1 activator drugs for Huntington's disease are years away from the market, of course, and the researchers note that more work will be needed to document Sirt1 activity in both normal and diseased brains.

- here's the release

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