Iron-Melanin Interaction in Substantia Nigra as the Neurotoxic Component of Parkinson’s Disease
In spite of the fashion to implicate environmental (e.g. MPTP-like) or endogenous (6-hydroxydopamine like) neurotoxins or an interaction between such factors and ageing as a process for nigra-striatal dopamine neuron loss, resulting in Parkinsonian syndrome, the primary cause of the idiopathic Parkinson’s Disease (PD) remains unknown. The nigra-striatal (SN) dopamine neurons of basal ganglia are very sensitive to many chemical insults, some of which have endogenous origin. Among these are the generation of oxygen free radicals formed from H2O2, generated by auto-oxidation and oxidative deamination of dopamine to melanin and deaminated products, respectively. The basal ganglia is endowed with highly active systems for scavenging of oxygen radicals. Among these are glutathione, glutathione peroxidase, superoxide dismutase and ascorbate, known to be present in relatively high concentrations. Theoretically a reduction in any of these could be highly damaging to the dopamine neurons (1). However, biochemical reactions which would promote the excessive formation of cytotoxic oxygen free radicals and which in turn can be highly damaging to the cell as a resultant lipid peroxidation should also be considered.Thus, ultimately, the balance between production and disposition of free radical may be the important factor. This has led a number of investigators to implicate oxidative stress as the primary cause of PD (2,3).
KeywordsLipid Peroxidation sUbstantia Nigra Oxygen Free Radical Dopamine Neuron Parkinsonian Brain
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