Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease

被引：60

作者：

Andreassen, OA

Ferrante, RJ

Huang, HM

Dedeoglu, A

Park, L

Ferrante, KL

Kwon, J

Borchelt, DR

Ross, CA

Gibson, GE

Beal, MF

机构：

[1] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY 10021 USA

[2] Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA

[5] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[6] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA

[7] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA

[8] Johns Hopkins Med Sch, Dept Pathol, Baltimore, MD USA

[9] Burke Med Res Inst, White Plains, NY USA

来源：

ANNALS OF NEUROLOGY | 2001年 / 50卷 / 01期

关键词：

D O I：

10.1002/ana.1085

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：112 / 117

页数：6

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