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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-7-13
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
1346
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26-42
pubmed:meshHeading
pubmed-meshheading:20513370-Animals, pubmed-meshheading:20513370-Apoptosis, pubmed-meshheading:20513370-Cytoskeleton, pubmed-meshheading:20513370-DNA, Complementary, pubmed-meshheading:20513370-Disease Progression, pubmed-meshheading:20513370-Gene Expression Profiling, pubmed-meshheading:20513370-Gene Expression Regulation, pubmed-meshheading:20513370-Immunohistochemistry, pubmed-meshheading:20513370-Inflammation, pubmed-meshheading:20513370-Lameness, Animal, pubmed-meshheading:20513370-Locomotion, pubmed-meshheading:20513370-MPTP Poisoning, pubmed-meshheading:20513370-Macaca mulatta, pubmed-meshheading:20513370-Male, pubmed-meshheading:20513370-Microarray Analysis, pubmed-meshheading:20513370-Oxidative Stress, pubmed-meshheading:20513370-Parkinson Disease, pubmed-meshheading:20513370-Promoter Regions, Genetic, pubmed-meshheading:20513370-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20513370-Signal Transduction, pubmed-meshheading:20513370-Synapses, pubmed-meshheading:20513370-Tyrosine 3-Monooxygenase, pubmed-meshheading:20513370-Wnt Proteins
pubmed:year
2010
pubmed:articleTitle
Gene expression profiling in progressively MPTP-lesioned macaques reveals molecular pathways associated with sporadic Parkinson's disease.
pubmed:affiliation
Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, 331-9530, Japan. t.ohnuki@po.rd.taisho.co.jp
pubmed:publicationType
Journal Article