title: Role of oxidative DNA damage in mitochondrial dysfunction and Huntington's disease pathogenesis.
abstract: Huntington's disease (HD) is a neurodegenerative disorder with an autosomal dominant expression pattern and typically a late-onset appearance. HD is a movement disorder with a heterogeneous phenotype characterized by involuntary dance-like gait, bioenergetic deficits, motor impairment, and cognitive and psychiatric deficits. Compelling evidence suggests that increased oxidative stress and mitochondrial dysfunction may underlie HD pathogenesis. However, the exact mechanisms underlying mutant huntingtin-induced neurological toxicity remain unclear. The objective of this paper is to review recent literature regarding the role of oxidative DNA damage in mitochondrial dysfunction and HD pathogenesis.
authors.affiliation: Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, P.O. Box 365067, San Juan, Puerto Rico 00936-5067. Electronic address: sylvette.ayala@upr.edu.
authors.forename: Sylvette
authors.initials: S
authors.lastname: Ayala-Peña
mesh_terms: D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress
chemical_list: D004272:DNA, Mitochondrial
keywords: 3-NPA; 3-nitropropionic acid; 7,8-dihydro-8-oxoguanine-DNA glycosylase; 8-OHdG; 8-hydroxydeoxyguanosine; AP; ARE; ATM; ATR; BER; DNA repair; FEN1; HD; Huntington’s disease; MMR; Mitochondrial DNA; Mitochondrial bioenergetics; Mitochondrial dysfunction; NF-E2-related factor 2; Nrf2; OGG1; Oxidative stress; PGC-1α; POL β; PPARγ; ROS; Rad3-related kinase; Sirt; antioxidant response element; apurinic/apyrimidinic; ataxia telangiectasia mutated kinase; base excision repair; flap endonuclease 1; mismatch repair; peroxisome proliferator-activated receptor-γ; peroxisome proliferator-activated receptor-γ coactivator-1 α; polymerase beta; reactive oxygen species; sirtuins