Abstract：
:Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of midbrain dopaminergic neurons. To gain an insight into the mechanisms underlying the progression of PD, gene expression analysis was performed using two different brain regions, the substantia nigra pars compacta (SN) and the striatum (STR), of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkey model of PD. 230 genes were differentially expressed in the MPTP-treated SN compared to control, whereas 452 genes showed altered expression in the MPTP-treated STR, implying that MPTP elicits more damages in the striatal gene expression than in the SN. Comparative data analysis of the transcription profiles on the PD patients and MPTP monkey models, and pathway analysis indicated several signaling pathways as possible routes to MPTP-induced neurodegeneration. Interestingly, the networks which associated with cytoskeletal stability, ubiquitin-proteasome system (UPS) and Wnt signaling gained prominence in our study. Further transcriptional regulatory network analysis suggested the association of the neuronal repressor REST (RE1-silencing transcription factor; NRSF) and androgen receptor with the dysregulation of the striatal genes. Our study suggests the possibility that the dysfunction of multi-network signaling may induce abnormalities in a diverse range of biological processes, such as synaptic function, cytoskeletal stability, survival and differentiation.
journal_name
Brain Resjournal_title
Brain researchauthors
Ohnuki T,Nakamura A,Okuyama S,Nakamura Sdoi
10.1016/j.brainres.2010.05.066subject
Has Abstractpub_date
2010-07-30 00:00:00pages
26-42eissn
0006-8993issn
1872-6240pii
S0006-8993(10)01270-9journal_volume
1346pub_type
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