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Mitochondrial defect in Huntington's disease caudate nucleus
Author(s) -
Gu M.,
Gash M. T.,
Mann V. M.,
JavoyAgid F.,
Cooper J. M.,
Schapira A. H. V.
Publication year - 1996
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.410390317
Subject(s) - caudate nucleus , huntington's disease , excitotoxicity , huntingtin , biology , respiratory chain , mitochondrial respiratory chain , mitochondrion , neurotoxin , medicine , endocrinology , microbiology and biotechnology , disease , biochemistry , programmed cell death , apoptosis
Although the Huntington's disease (HD) gene defect has been identified, the structure and function of the abnormal gene product and the pathogenetic mechanisms involved in producing death of selective neuronal populations are not understood. Indirect evidence from several sources indicates that a defect of energy metabolism and consequent excitotoxicity are involved in HD. Toxin models of HD may be induced by 3‐nitropropionic acid or malonate, both inhibitors of succinate dehydrogenase, complex II of the mitochondrial respiratory chain. We analyzed mitochondrial respiratory chain function in the caudate nucleus (n = 10) and platelets (n = 11) from patients with HD. In the caudate nucleus, severe defects of complexes II and III (53–59%, p < 0.0005) and a 32–38% ( p < 0.01) deficiency of complex IV activity were demonstrated. No deficiencies were found in platelet mitochondrial function. The mitochondrial defect identified in HD caudate parallels that induced by HD neurotoxin models and further supports the role of abnormal energy metabolism in HD. The relationship of the mitochondrial defect to the role of huntingtin is not known.