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 - http://www.scopus.com/inward/record.url?scp=33846905913&partnerID=8YFLogxK
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 -