The copper chelator, D-penicillamine, does not attenuate MPTP induced dopamine depletion in mice.
In MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-hydroxydopamine induced dopaminergic neurotoxicity and Parkinson's disease iron accumulates in substantia nigra pars compacta which has been suggested to participate in oxidative stress induced neurodegeneration. Pretreatment with iron chelators desferal, clioquinol, VK-28 and M30 are neuroprotective in both models. To determine the specificity of chelation neuroprotective activity we have examined the effect of D-penicillamine, a relatively specific copper chelator, in the mice model of MPTP-induced dopamine depletion. Our studies show that D-penicillamine, employed for removal of copper in Wilson disease is relatively weak in preventing dopaminergic neurotoxicity induced by MPTP, as compared to iron chelators previously studied. The results indicate that for prevention of MPTP-induced dopamine depletion and dopamine neurodegeneration, iron rather than copper chelation may be more effective and specific.
Youdim
M B H
MB
Eve Topf and US National Parkinson Foundation, Centers of Excellence For Neurodegenerative Diseases Research, Technion-Rappaport Family Faculty of Medicine, Haifa, Israel. Youdim@tx.technion.ac.il
Grünblatt
E
E
Mandel
S
S
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity*; D007501:Iron / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010396:Penicillamine / Q000494:pharmacology*; D020156:Salicylic Acid / Q000494:pharmacology
D002614:Chelating Agents; D015259:Dopamine Agents; D018696:Neuroprotective Agents; D007501:Iron; D010396:Penicillamine; D020156:Salicylic Acid; D004298:Dopamine; D000111:Acetylcysteine