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Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia
Author(s) -
Browne Susan E.,
Bowling Allen C.,
Macgarvey Usha,
Baik M. Jay,
Berger Stephanie C.,
Muquit Miratul M. K.,
Bird Edward D.,
Beal M. Flint
Publication year - 1997
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.410410514
Subject(s) - putamen , basal ganglia , huntington's disease , huntingtin , medicine , glyceraldehyde 3 phosphate dehydrogenase , endocrinology , superoxide dismutase , biology , neurodegeneration , oxidative phosphorylation , cerebellum , oxidative stress , biochemistry , enzyme , central nervous system , dehydrogenase , disease
The etiology of the selective neuronal death that occurs in Huntington's disease (HD) is unknown. Several lines of evidence implicate the involvement of energetic defects and oxidative damage in the disease process, including a recent study that demonstrated an interaction between huntingtin protein and the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). Using spectrophotometric assays in postmortem brain tissue, we found evidence of impaired oxidative phosphorylation enzyme activities restricted to the basal ganglia in HD brain, while enzyme activities were unaltered in three regions relatively spared by HD pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase‐corrected complex II‐III activity was markedly reduced in both HD caudate (−29%) and putamen (−67%), and complex IV activity was reduced in HD putamen (−62%). Complex I and GAPDH activities were unaltered in all regions examined. We also measured levels of the oxidative damage product 8‐hydroxydeoxyguanosine (OH 8 dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH 8 dG levels were significantly increased in HD caudate. Cytosolic SOD activity was slightly reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity was unaltered in these regions. These results further support a role for metabolic dysfunction and oxidative damage in the pathogenesis of HD.