A growing body of evidence has suggested that oxidative stress is likely to play major a role in neuronal cell loss associated with PD. Alterations in levels of accessories reactive iron and the peroxide-scavenging antioxidant glutathione (GSH) in the PD brain have both been postulated to contribute to the loss of dopaminergic neurons of the substantia nigra (SN) associated with the disease via oxidative stress-related mechanisms. The investigators currently have two existing NIH grants to explore the effects of chronic alterations in brain iron levels via neonatal iron feeding in conjunction with transgenic mouse lines which display altered SN expression levels of the protective iron-storage protein ferritin and SN GSH levels via transgenic lines expressing antisense message against the glutathione-synthesizing enzyme glutamyl cysteine synthetase (antiGCS). These models are presently being used in conjunction with the well-established MPTP toxicity model of PD to test whether chronic alterations in SN iron or GSH levels alters age-related increases in nigrostriatal degeneration compound and whether this involves alterations of levels of either oxidative stress or mitochondrial dysfunction.
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