Related Experiment Video
Updated: Aug 8, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
The copper chelator, D-penicillamine, does not attenuate MPTP induced dopamine depletion in mice
M B H Youdim1, E Grünblatt, S Mandel
1Eve 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
Abstract:
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.
Insights
Iron chelation, not copper chelation, appears more effective in preventing neurodegeneration in Parkinson's disease models. This suggests iron plays a key role in oxidative stress contributing to dopamine neuron loss.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Iron accumulation in the substantia nigra pars compacta is implicated in Parkinson's disease (PD) pathogenesis.
- Iron is suspected to contribute to oxidative stress and subsequent neurodegeneration in PD models.
- Previous studies showed neuroprotection with iron chelators in MPTP and 6-hydroxydopamine models.
Purpose of the Study:
- To investigate the specificity of chelation therapy for neuroprotection.
- To compare the efficacy of a copper chelator versus iron chelators in MPTP-induced neurotoxicity.
- To determine if iron or copper chelation is more effective in preventing dopaminergic neurodegeneration.
Main Methods:
- Utilized the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease.
- Administered D-penicillamine, a copper-specific chelator, as a pretreatment.
- Assessed the effect of D-penicillamine on dopamine depletion and neurodegeneration.
Main Results:
- D-penicillamine showed limited neuroprotective effects against MPTP-induced dopaminergic neurotoxicity.
- The neuroprotective efficacy of D-penicillamine was significantly weaker compared to previously studied iron chelators.
- MPTP-induced dopamine depletion was not substantially prevented by copper chelation.
Conclusions:
- Iron chelation appears more effective and specific than copper chelation for preventing MPTP-induced dopaminergic neurotoxicity.
- These findings highlight the critical role of iron in the oxidative stress mechanisms underlying Parkinson's disease.
- Targeting iron accumulation may represent a more promising therapeutic strategy for Parkinson's disease.
Related Concept Videos
01:24Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of its...
01:26Anticholinesterase Agents: Poisoning and Treatment
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is slower than the...