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Novel Chelators for Central Nervous System Disorders That Involve Alterations in the Metabolism of Iron and Other Metal Ions
DES R. RICHARDSON
Iron Metabolism and Chelation Program, Children's Cancer Institute Australia for Medical Research, Randwick, Sydney, New South Wales, Australia
Address for correspondence: Dr. D. R. Richardson, Iron Metabolism and Chelation Program, Children's Cancer Institute Australia for Medical Research, High Street (P. O. Box 81), Randwick, Sydney, New South Wales, 2031 Australia. Voice: +61-2-9314-7924; fax: +61-2-9382-1850. d.richardson{at}ccia.org.au
Ann N.Y. Acad. Sci. 1012: 326-341 (2004).
Recent evidence suggests that iron (Fe) and other metals play a role in a number of neurodegenerative diseases including Friedreich's ataxia, Alzheimer's disease, Huntington's disease, and Parkinson's disease. In this review, the role of Fe and other metals in the pathology of these conditions is assessed and the potential of Fe chelators for treatment is discussed. Lipophilic chelators have been designed that may be capable of crossing the blood-brain barrier, a property lacking in desferrioxamine (DFO), a chelator in widespread clinical use. A far less commonly used chelator, clioquinol, has already shown activity in vivo in animal models and also in Alzheimer's disease patients. Considering that there is no effective treatment for many neurological diseases, the therapeutic use of lipophilic Fe chelators remains a potential strategy that requires investigation. In particular, we discuss the development of several series of aroylhydrazone chelators that could have high potential in the treatment of these diseases.
Key Words: Alzheimer's disease • clioquinol • Friedreich's ataxia • Huntington's disease • iron • iron chelators • iron metabolism • Parkinson's disease • pyridoxal isonicotinoyl hydrazone; 2-pyridylcarboxaldehyde isonicotinoyl hydrazone
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