Iron: a new target for pharmacological intervention in neurodegenerative diseases.
Iron (Fe) is an essential element that is imperative for the redox-driven processes of oxygen transport, electron transport, and DNA synthesis. However, in the absence of appropriate storage or chelation, excess-free Fe readily participates in the formation of toxic-free radicals, inducing oxidative stress and apoptosis. A growing body of evidence suggests that Fe may play some role in neurodegenerative diseases such as Huntington disease, Alzheimer's disease, Parkinson's disease, and particularly Friedreich's ataxia. This review examines the role of Fe in the pathology of these conditions and the potential use of Fe chelators as therapeutic agents for the treatment of neurodegenerative disorders. Consideration is given to the features that comprise a clinically successful Fe chelator, with focus on the development of ligands such as desferrioxamine, clioquinol, pyridoxal isonicotinoyl hydrazone, and other novel aroylhydrazones.
Whitnall
Megan
M
Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia.
Richardson
Des R
DR
D000818:Animals; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019189:Iron Metabolism Disorders / Q000188:drug therapy / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*
D007502:Iron Chelating Agents; D007501:Iron