title: Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington's disease.
abstract: Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder, characterized by an array of different psychiatric manifestations, cognitive decline and choreiform movements. The underlying molecular genetic defect is an expanded trinucleotide (CAG)n repeat encoding a polyglutamine stretch in the N-terminus of the huntingtin protein. The mechanisms by which mutant huntingtin causes neuronal dysfunction and degeneration are not fully understood. Nevertheless, impaired ubiquitin-proteasome activity, defective autophagy-lysosomal function, transcriptional dysregulation, oxidative stress, apoptosis, mitochondrial and metabolic dysfunction, and abnormal protein-protein interaction have been shown to play important roles in the pathogenesis of HD. Neurons are energy-demanding and more susceptible to energetic failure and oxidative damage than other types of cell. Given that mitochondria play a central role in both processes of metabolism and oxidative stress, and increasing direct evidence shows mitochondrial abnormalities in both HD mouse models and patients, this article will review the studies of mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in HD, and discuss the potential therapeutics targeting these abnormalities.
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. cmchen@cgmh.org.tw
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009574:Nitro Compounds; D018384:Oxidative Stress; D011422:Propionates; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid; D002118:Calcium