title: Mitochondrial metals as a potential therapeutic target in neurodegeneration.
abstract: Transition metals are critical for enzyme function and protein folding, but in excess can mediate neurotoxic oxidative processes. As mitochondria are particularly vulnerable to oxidative damage due to radicals generated during ATP production, mitochondrial biometal homeostasis must therefore be tightly controlled to safely harness the redox potential of metal enzyme cofactors. Dysregulation of metal functions is evident in numerous neurological disorders including Alzheimer's disease, stroke, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and Friedrich's ataxia. This review describes the mitochondrial metal defects in these disorders and highlights novel metal-based therapeutic approaches that target mitochondrial metal homeostasis in neurological disorders.
authors.affiliation: Department of Pathology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: A
authors.initials: A
authors.lastname: Grubman
authors.forename: A R
authors.initials: AR
authors.lastname: White
authors.forename: J R
authors.initials: JR
authors.lastname: Liddell
mesh_terms: D002412:Cations / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D058990:Molecular Targeted Therapy / Q000379:methods*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology*; D028561:Transition Elements / Q000378:metabolism*
chemical_list: D002412:Cations; D002614:Chelating Agents; D028561:Transition Elements
keywords: Cu(atsm); Mn porphyrins; biometal homeostasis; curcumin; deferiprone; mitochondria; neurodegeneration; stroke