Mitochondrial metals as a potential therapeutic target in neurodegeneration

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 tigh...

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Bibliographic Details
Published in:British journal of pharmacology 2014-04, Vol.171 (8), p.2159-2173
Main Authors: Grubman, A, White, A R, Liddell, J R
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
biometal homeostasis
Cations - therapeutic use
Chelating Agents - therapeutic use
Cu(atsm)
curcumin
deferiprone
Enzymes
Homeostasis
Humans
Metals
mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria - physiology
Mn porphyrins
Molecular Targeted Therapy - methods
neurodegeneration
Neurodegenerative Diseases - drug therapy
Neurodegenerative Diseases - physiopathology
stroke
Themed Issue: Mitochondrial Pharmacology: Energy, Injury & Beyond
Transition Elements - metabolism
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Summary: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. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.12513