Mitochondrial functional alterations in relation to pathophysiology of Huntington's disease.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease which is characterized by psychiatric symptoms, involuntary choreiform movements and dementia with maximum degeneration occurring in striatum and cerebral cortex. Several studies implicate mitochondrial dysfunction to the selective neurodegeneration happening in this disorder. Calcium buffering imbalance and oxidative stress in the mitochondria, critically impaired movement across axons and abnormal fission or fusion of this organelle in the cells are some of the salient features that results in the loss of mitochondrial electron transport chain (ETC) complex function in HD. Although several models involving mutant huntingtin, excitotoxins and mitochondrial complex-II inhibitors have been used to explore the disease, it is not clear how disturbances in mitochondrial functioning is associated with such selective neurodegeneration, or in the expression of huntingtonian phenotypes in animals or man. We have carefully assessed various mitochondrial abnormalities observed in human patient samples, postmortem HD brains, cellular, vertebrate and invertebrate models of the disease, to conclude that ETC dysfunction is an integral part of the disease and justify a causal role of mitochondrial ETC dysfunction for the genesis of this disorder.
Pandey
Mritunjay
M
Division of Cell Biology & Physiology, Laboratory of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology (CSIR), 4, Raja S. C. Mullick Road, Kolkata, 700 032, India.
Mohanakumar
Kochupurackal P
KP
Usha
Rajamma
R
D000818:Animals; D001921:Brain / Q000473:pathology; D045222:Electron Transport Chain Complex Proteins; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D009410:Nerve Degeneration
D045222:Electron Transport Chain Complex Proteins
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