Identification of glutathione S-transferase pi as a protein involved in Parkinson disease progression.
Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique. Approximately 100 proteins displayed significant differences in their relative abundances between PD patients at various stages and controls; three of these proteins were validated using independent techniques. One of the confirmed proteins, glutathione S-transferase Pi, was further investigated in cellular models of PD, demonstrating that its level was intimately associated with several critical cellular processes that are directly related to neurodegeneration in PD. These results have, for the first time, suggested that the levels of glutathione S-transferase Pi may play an important role in modulating the progression of PD.
Shi
Min
M
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
Bradner
Joshua
J
Bammler
Theo K
TK
Eaton
David L
DL
Zhang
Jianpeng
J
Ye
ZuCheng
Z
Wilson
Angela M
AM
Montine
Thomas J
TJ
Pan
Catherine
C
Zhang
Jing
J
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D018450:Disease Progression; D005260:Female; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection
D051549:Glutathione S-Transferase pi; D048670:MAP Kinase Kinase 4