Tom Fagan reported in previous research news that enhancing PGC-1α expression may be beneficial in the treatment of Huntington disease. He cites the research by Krainc and colleagues that CREB is displaced from the coactivator's promoter by mutant htt (1). Liang and colleagues find that 3T3 fibroblast cells overexpressing PGC-1α have increased ATP levels and are more resistant to oxidative stress (2). This study by Kovtun et al. would seem to suggest that this inhibition of PGC-1α by mutant huntingtin sets the scene for future CAG expansion by providing the stimulus for this "toxic oxidation cycle."

Struewing et al. find that lithium increases PGC-1α in primary bovine aortic endothelial cells (3). It's of interest that it has also been shown to promote neuronal survival and proliferation in the quinolinic acid model of Huntington disease (4). Might it also prevent CAG expansion?

References:
1. See ARF related news story.

2. Liang H, Bai Y, Li Y, Richardson A, Ward WF. PGC-1{alpha}-Induced Mitochondrial Alterations in 3T3 Fibroblast Cells. Ann N Y Acad Sci. 2007 Apr;1100:264-79. Abstract

3. Struewing IT, Barnett CD, Tang T, Mao CD. Lithium increases PGC-1alpha expression and mitochondrial biogenesis in primary bovine aortic endothelial cells. FEBS J. 2007 Apr 20; [Epub ahead of print] Abstract

4. Senatorov VV, Ren M, Kanai H, Wei H, Chuang DM. Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease. Mol Psychiatry. 2004 Apr;9(4):371-85. Abstract

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