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Systems-based analyses of brain regions functionally impacted in Parkinson's disease reveals underlying causal mechanisms.

Authors :
Brigit E Riley
Shyra J Gardai
Dorothea Emig-Agius
Marina Bessarabova
Alexander E Ivliev
Birgitt Schüle
Jeff Alexander
William Wallace
Glenda M Halliday
J William Langston
Scott Braxton
Ted Yednock
Thomas Shaler
Jennifer A Johnston
Source :
PLoS ONE, Vol 9, Iss 8, p e102909 (2014)
Publication Year :
2014
Publisher :
Public Library of Science (PLoS), 2014.

Abstract

Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum, and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. We undertook functional and causal pathway analysis of gene expression and proteomic alterations in these three regions, and the data revealed pathways that correlated with disease progression. In addition, microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release, and these and other changes were reflected across all brain regions. Importantly, subsets of these changes were replicated in Parkinson's disease blood; suggesting peripheral tissue may provide important avenues for understanding and measuring disease status and progression. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany functional loss and alpha-synuclein pathology in Parkinson's disease, and may be instrumental to understand, diagnose and follow Parkinson's disease progression.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
9
Issue :
8
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.75c932800ae34e25a56cae5f4cee04c5
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0102909