Glutathione is an abundant intracellular thiol antioxidant whose levels are reduced both in Parkinson's disease itself and in a widely used animal model of the disorder, systemic MPTP administration. Previous in vitro work from our laboratory has suggested that glutathione depletion may be directly responsible for mitochondrial dysfunction, which ultimately leads to dopaminergic cell death associated with the disease. Here, we demonstrate the ability of gamma-glutamylcysteine ethyl ester, a lipid permeable derivative of the major substrate for scavenger glutathione synthesis, to counteract glutathione loss and neurodegeneration associated with in vitro and in vivo administration of MPTP or its derivatives. This data suggests that prevention of glutathione depletion is a likely therapeutic target for the disease.
|Number of pages||5|
|State||Published - Jul 10 2006|
Bibliographical noteFunding Information:
This work was supported in part by NIH grants to D.A.B. [AG-10836; AG-05119] and to J.A. [AG-12141 and NS-045615].
- Parkinson's disease
- Tyrosine hydroxylase
- γ-Glutamylcysteinyl ethyl ester
ASJC Scopus subject areas
- Neuroscience (all)