PMID: 10668410: Neuroprotection in PD with iron chelators

[janet marie paterson <janet313@xxxxxxxxxxx>]

The pivotal role of iron in NF-kappa B activation and nigrostriatal
dopaminergic neurodegeneration. Prospects for neuroprotection in
Parkinson's disease with iron chelators.

R-Apomorphine (APO) the catechol-derived dopamine D1-D2 receptor agonist has 
been shown to be highly potent iron chelator and radical scavenger and 
inhibitor of membrane lipid peroxidation in vitro, in vivo and in cell culture 
employing PC12 cells.

Its potency has been compared to the prototype iron chelator desferrioxamine 
(desferal), dopamine, nifedipine and dopamine D2 receptor agonists, 
bromocriptine, lisuride, pergolide and pramipexole.

APO also inhibits brain and mitochondrial protein oxidation.

In vivo APO protects against MPTP 
(N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)- induced striatal dopaminergic 
neurodegeneration in C57 black mice with as low as 5 mg/kg.

APO is a reversible competitive inhibitor of monoamine oxidase (MAO) A and B 
with IC50 values of 93 and 214 uM, respectively.

The iron chelating and radical scavenging actions of desferal and APO explains 
their ability to inhibit iron and 6-hydroxydopamine (6-OHDA)-induced 
neurodegeneration and activation of redox-sensitive transcription factor 
NF-kappa B and the subsequent transactivation of promoters of genes involved in 
inflammatory cytokines.

Iron is thought to play a pivotal role in neurodegeneration, and APO may be an 
ideal drug to investigate neuroprotection in Parkinson's disease where iron and 
oxidative stress have been implicated in the pathogenesis of nigrostriatal 
dopamine neuron degeneration.


Ann N Y Acad Sci 1999;890:7-25
Youdim MB, Grunblatt E, Mandel S
Technion, Faculty of Medicine, Eve Topf, Haifa, Israel.
<A HREF=";>youdim@xxxxxxxxxxxxxxxxx</A>
PMID: 10668410, UI: 20133589

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janet paterson
52 now / 41 dx / 37 onset
a new voice: 
613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0