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Scientists identify switch for brain's natural anti-oxidant defense

BOSTON--Scientists at Dana-Farber Cancer Institute report they have found how the brain turns on a system designed to protect its nerve cells from toxic "free radicals," a waste product of cell metabolism that has been implicated in some degenerative brain diseases, heart attacks, strokes, cancer, and aging.

Potentially, the researchers say, it may be possible to use drugs to strengthen the anti-oxidant system in the brain as a treatment for presently incurable diseases like Parkinson's, Huntington's, and Alzheimer's and possibly other maladies.

Dana-Farber's Bruce Spiegelman, PhD, and colleagues, using a mouse model, discovered that a regulatory protein, PGC-1a, switches on the anti-oxidant system when free radicals, or reactive oxygen species, begin to accumulate. It's believed that some brain diseases involve a failure of the protective system, and the authors report that turning on PGC-1a to high levels in cultured cells protected them against nerve toxins. The findings will be reported in the Oct. 20 issue of the journal Cell.

"This could have broad implications for the many diseases in which reactive oxygen species are implicated," said Spiegelman. Anti-oxidant supplements have been used with some success in patients with neurodegenerative diseases, but Spiegelman noted that the process sparked by PGC-1a "is how nature does it."

Researchers currently are screening drugs in search of compounds that could spur PGC-1a expression in brain cells, as well as exploring whether any harmful side effects might result. PGC-1a is a transcriptional co-activator discovered in Spiegelman's Dana-Farber laboratory in 1998. It has subsequently been found to play a master regulatory role in metabolic processes and muscle function, as well as being a culprit in diabetes.

The report establishes for the first time that PGC-1a both drives the mitochondria to make energy and triggers the cleanup of toxic free radicals that accumulate in
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
19-Oct-2006


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