title: Targeting mitochondrial metal dyshomeostasis for the treatment of neurodegeneration.
abstract: Mitochondrial impairment and metal dyshomeostasis are suggested to be associated with many neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and Friedreich's ataxia. Treatments aimed at restoring metal homeostasis are highly effective in models of these diseases, and clinical trials hold promise. However, in general, the effect of these treatments on mitochondrial metal homeostasis is unclear, and the contribution of mitochondrial metal dyshomeostasis to disease pathogenesis requires further investigation. This review describes the role of metals in mitochondria in health, how mitochondrial metals are disrupted in neurodegenerative diseases, and potential therapeutics aimed at restoring mitochondrial metal homeostasis and function.
authors: Department of Pathology, University of Melbourne, Victoria 3010, Australia.
authors: Jeffrey R
authors: JR
authors: Liddell
mesh_terms: D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002986:Clinical Trials as Topic; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism; D008667:Metalloproteins / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000628:therapy*; D015125:Oxyquinoline / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D008667:Metalloproteins; C000606290:SOD1 protein, human; D015125:Oxyquinoline; D007501:Iron; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Alzheimer's disease; Cu-ATSM; Friedreich's ataxia; Huntington's disease; Parkinson's disease; amyotrophic lateral sclerosis; chelating agents; deferiprone; mitochondria; superoxide dismutase