Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease |
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Authors: | Kaur Deepinder Yantiri Ferda Rajagopalan Subramanian Kumar Jyothi Mo Jun Qin Boonplueang Rapee Viswanath Veena Jacobs Russell Yang Lichuan Beal M Flint DiMonte Dino Volitaskis Irene Ellerby Lisa Cherny Robert A Bush Ashley I Andersen Julie K |
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Affiliation: | Buck Institute for Age Research, Novato, CA 94945, USA. |
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Abstract: | Studies on postmortem brains from Parkinson's patients reveal elevated iron in the substantia nigra (SN). Selective cell death in this brain region is associated with oxidative stress, which may be exacerbated by the presence of excess iron. Whether iron plays a causative role in cell death, however, is controversial. Here, we explore the effects of iron chelation via either transgenic expression of the iron binding protein ferritin or oral administration of the bioavailable metal chelator clioquinol (CQ) on susceptibility to the Parkinson's-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrapyridine (MPTP). Reduction in reactive iron by either genetic or pharmacological means was found to be well tolerated in animals in our studies and to result in protection against the toxin, suggesting that iron chelation may be an effective therapy for prevention and treatment of the disease. |
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