TY - JOUR T1 - Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4389 LP - 4397 DO - 10.1523/JNEUROSCI.20-12-04389.2000 VL - 20 IS - 12 AU - Robert J. Ferrante AU - Ole A. Andreassen AU - Bruce G. Jenkins AU - Alpaslan Dedeoglu AU - Stefan Kuemmerle AU - James K. Kubilus AU - Rima Kaddurah-Daouk AU - Steven M. Hersch AU - M. Flint Beal Y1 - 2000/06/15 UR - http://www.jneurosci.org/content/20/12/4389.abstract N2 - Huntington's disease (HD) is a progressive neurodegenerative illness for which there is no effective therapy. We examined whether creatine, which may exert neuroprotective effects by increasing phosphocreatine levels or by stabilizing the mitochondrial permeability transition, has beneficial effects in a transgenic mouse model of HD (line 6/2). Dietary creatine supplementation significantly improved survival, slowed the development of brain atrophy, and delayed atrophy of striatal neurons and the formation of huntingtin-positive aggregates in R6/2 mice. Body weight and motor performance on the rotarod test were significantly improved in creatine-supplemented R6/2 mice, whereas the onset of diabetes was markedly delayed. Nuclear magnetic resonance spectroscopy showed that creatine supplementation significantly increased brain creatine concentrations and delayed decreases in N-acetylaspartate concentrations. These results support a role of metabolic dysfunction in a transgenic mouse model of HD and suggest a novel therapeutic strategy to slow the pathological process. ER -