Concordant signaling pathways produced by pesticide exposure in mice correspond to pathways identified in human Parkinson's disease.

PloS One
Seema GollamudiM Flint Beal

Abstract

Parkinson's disease (PD) is a neurodegenerative disease in which the etiology of 90 percent of the patients is unknown. Pesticide exposure is a major risk factor for PD, and paraquat (PQ), pyridaben (PY) and maneb (MN) are amongst the most widely used pesticides. We studied mRNA expression using transcriptome sequencing (RNA-Seq) in the ventral midbrain (VMB) and striatum (STR) of PQ, PY and paraquat+maneb (MNPQ) treated mice, followed by pathway analysis. We found concordance of signaling pathways between the three pesticide models in both the VMB and STR as well as concordance in these two brain areas. The concordant signaling pathways with relevance to PD pathogenesis were e.g. axonal guidance signaling, Wnt/β-catenin signaling, as well as pathways not previously linked to PD, e.g. basal cell carcinoma, human embryonic stem cell pluripotency and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Human PD pathways previously identified by expression analysis, concordant with VMB pathways identified in our study were axonal guidance signaling, Wnt/β-catenin signaling, IL-6 signaling, ephrin receptor signaling, TGF-β signaling, PPAR signaling and G-protein coupled receptor signaling. Human PD pathwa...Continue Reading

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Citations

Oct 12, 2013·Journal of Molecular Cell Biology·Daniel C Berwick, Kirsten Harvey
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Datasets Mentioned

BETA
GSE36232

Methods Mentioned

BETA
RNA-Seq
PCR
Assay
nuclear translocation
environmental
ESR
ubiquitination

Software Mentioned

BWA
Ingenuity
Stereo Investigator
STR
IPA
R
Ingenuity Pathway Analysis ( IPA )

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