Mitochondrial defect in Huntington's disease caudate nucleus

Annals of Neurology - Tập 39 Số 3 - Trang 385-389 - 1996
Muxin Gu1, M. T. Gash2, V. M. Mann2, F. Javoy‐Agid3, Jonathan M. Cooper2, Anthony H.V. Schapira2
1Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, United Kingdom
2Deparment of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, United Kingdom
3INSERM ULXS, Paris, France

Tóm tắt

AbstractAlthough 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.

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Annals of Neurology

Tập 39 Số 3

385-389

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