title: Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease.
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.
authors.affiliation: Buck Institute for Age Research, Novato, CA 94945, USA.
authors.forename: Deepinder
authors.initials: D
authors.lastname: Kaur
authors.forename: Ferda
authors.initials: F
authors.lastname: Yantiri
authors.forename: Subramanian
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Jyothi
authors.initials: J
authors.lastname: Kumar
authors.forename: Jun Qin
authors.initials: JQ
authors.lastname: Mo
authors.forename: Rapee
authors.initials: R
authors.lastname: Boonplueang
authors.forename: Veena
authors.initials: V
authors.lastname: Viswanath
authors.forename: Russell
authors.initials: R
authors.lastname: Jacobs
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Dino
authors.initials: D
authors.lastname: DiMonte
authors.forename: Irene
authors.initials: I
authors.lastname: Volitaskis
authors.forename: Lisa
authors.initials: L
authors.lastname: Ellerby
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Julie K
authors.initials: JK
authors.lastname: Andersen
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D007464:Clioquinol / Q000627:therapeutic use; D004298:Dopamine / Q000032:analysis; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D006719:Homovanillic Acid / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control*; D011401:Promoter Regions, Genetic; D051381:Rats; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D007502:Iron Chelating Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D007464:Clioquinol; D005293:Ferritins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid