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GSTpi expression mediates dopaminergic neuron sensitivity in experimental parkinsonism.

ABSTRACT: The cause of 95% of Parkinson's disease (PD) cases is unknown. It is hypothesized that PD arises from an interaction of free-radical-generating agents with an underlying genetic susceptibility to these compounds. Here we use the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism to examine the role of a dual function protein, GSTpi, in dopaminergic neuron death. GSTpi is the only GST family member expressed in substantia nigra neurons. GSTpi reduction by pharmacological blockade, RNA inhibition, and gene targeting increases sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, suggesting that differential expression of GSTpi contributes to the sensitivity to xenobiotics in the substantia nigra and may influence the pathogenesis of reactive oxygen species-induced neurological disorders including PD.

SUBMITTER: Smeyne M

PROVIDER: S-EPMC1785361 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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GSTpi expression mediates dopaminergic neuron sensitivity in experimental parkinsonism.

Smeyne Michelle M Boyd Justin J Raviie Shepherd Kennie K Jiao Yun Y Pond Brooks Barnes BB Hatler Matthew M Wolf Roland R Henderson Colin C Smeyne Richard Jay RJ

Proceedings of the National Academy of Sciences of the United States of America 20070131 6

The cause of 95% of Parkinson's disease (PD) cases is unknown. It is hypothesized that PD arises from an interaction of free-radical-generating agents with an underlying genetic susceptibility to these compounds. Here we use the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism to examine the role of a dual function protein, GSTpi, in dopaminergic neuron death. GSTpi is the only GST family member expressed in substantia nigra neurons. GSTpi reduction by pharmacological blockade, ...[more]

PMID: 17267597

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