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Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease
Author(s) -
Andreassen Ole A.,
Ferrante Robert J.,
Huang HsuehMeei,
Dedeoglu Alpaslan,
Park Larry,
Ferrante Kimberly L.,
Kwon Jennifer,
Borchelt David R.,
Ross Christopher A.,
Gibson Gary E.,
Beal M. Flint
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1085
Subject(s) - huntington's disease , genetically modified mouse , transgene , huntingtin , pyruvate dehydrogenase complex , disease , pathogenesis , atrophy , endocrinology , medicine , neuroscience , biology , gene , biochemistry , enzyme
Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171‐82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD.