GSTπ expression mediates dopaminergic neuron sensitivity in experimental parkinsonism

TY - JOUR

T1 - GSTπ expression mediates dopaminergic neuron sensitivity in experimental parkinsonism

AU - Smeyne, Michelle

AU - Boyd, Justin

AU - Shepherd, Kennie Raviie

AU - Jiao, Yun

AU - Pond, Brooks Barnes

AU - Hatler, Matthew

AU - Wolf, Roland

AU - Henderson, Colin

AU - Smeyne, Richard Jay

PY - 2007/2/6

Y1 - 2007/2/6

N2 - 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, GSTπ, in dopaminergic neuron death. GSTπ is the only GST family member expressed in substantia nigra neurons. GSTπ 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 GSTπ contributes to the sensitivity to xenobiotics in the substantia nigra and may influence the pathogenesis of reactive oxygen species-induced neurological disorders including PD.

AB - 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, GSTπ, in dopaminergic neuron death. GSTπ is the only GST family member expressed in substantia nigra neurons. GSTπ 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 GSTπ contributes to the sensitivity to xenobiotics in the substantia nigra and may influence the pathogenesis of reactive oxygen species-induced neurological disorders including PD.

KW - Detoxification

KW - Glutathione

KW - Oxidative stress

KW - Parkinson's disease

KW - Substantia nigra

UR - https://www.scopus.com/pages/publications/33846905913

U2 - 10.1073/pnas.0610978104

DO - 10.1073/pnas.0610978104

M3 - Article

C2 - 17267597

AN - SCOPUS:33846905913

SN - 0027-8424

VL - 104

SP - 1977

EP - 1982

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 6

ER -