Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia

Ann Neurol. 1997 May;41(5):646-53. doi: 10.1002/ana.410410514.


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 (OH8dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH8dG 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basal Ganglia / metabolism*
  • Cerebellum / metabolism
  • Cerebral Cortex / metabolism
  • DNA / analysis
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • Huntington Disease / metabolism*
  • In Vitro Techniques
  • Mitochondria / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Oxidation-Reduction
  • Reference Values
  • Spectrophotometry
  • Stress, Physiological / metabolism
  • Superoxide Dismutase / metabolism


  • DNA
  • Superoxide Dismutase
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • NAD(P)H Dehydrogenase (Quinone)