Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease
- 26 June 2001
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 50 (1) , 112-116
- https://doi.org/10.1002/ana.1085
Abstract
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.Keywords
This publication has 21 references indexed in Scilit:
- Decreased expression of striatal signaling genes in a mouse model of Huntington's diseaseHuman Molecular Genetics, 2000
- Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin [published erratum appears in Hum Mol Genet 1999 May;8(5):943]Human Molecular Genetics, 1999
- Stabilization of the pyruvate dehydrogenase E1α subunit by dichloroacetateNeurology, 1998
- Effects of dichloroaeetate in three patients with MELASNeurology, 1998
- Energy metabolism defects in Huntington's disease and effects of coenzyme Q10Annals of Neurology, 1997
- Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic MiceCell, 1996
- Improvement of lesions shown on MRI and CT scan by administration of dichloroacetate in patients with Leigh syndromeJournal of the Neurological Sciences, 1995
- The role of cytosolic free calcium in the regulation of pyruvate dehydrogenase in synaptosomesNeurochemical Research, 1994
- Evidence for irnnairment of energy metabofism in vivo in Huntington's disease using localized 1H NMR spectroscopyNeurology, 1993
- Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brainAnnals of Neurology, 1983