Identification of glial-cell-line-derived neurotrophic factor-regulated proteins of striatum in mouse model of Parkinson disease.
Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for dopaminergic neurons, and hence serves as a therapeutic candidate for the treatment of Parkinson's disease. However, despite the potential clinical and physiological importance of GDNF, its mechanism of action is unclear. Therefore, we employed a state-of-the-art proteomic technique, DIGE, along with MS and a bioinformatics tool called Database for Annotation, Visualization and Integrated Discovery (DAVID), to profile proteome changes in the parkinsonian mouse striatum after GDNF challenge. Forty-six unique differentially expressed proteins were successfully identified, which were found either up-regulated and/or down-regulated at the two time points 4 and 72 h compared with the control. Proteins involved in cell differentiation and system development formed the largest part of the proteins regulated under GDNF. Furthermore, the aberrant expression of HSPs and mitochondria-associated proteins were noticeable. Moreover, mitochondrial stress 70 protein and heat shock cognate 71 kDa protein, whose relative levels increased significantly in GDNF-treated striatum, were further evaluated with Western blot and RT-PCR, demonstrating a good agreement with quantitative proteomic data. These data will provide some clues for understanding the mechanisms by which GDNF promotes the survival of dopaminergic neurons.
Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.
Zhen
Z
Hong
Jun
J
Liu
Li
L
Xia
Jing
J
Pan
Qin
Q
Xiao
Guoqiang
G
Lu
Liang
L
Liang
Sheng-Di
SD
Chen