Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms

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...

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Main Authors:	Riley, Brigit E., Gardai, Shyra J., Emig-Agius, Dorothea, Bessarabova, Marina, Ivliev, Alexander E., Schüle, Birgit, Alexander, Jeff, Wallace, William, Halliday, Glenda M., Langston, J. William, Braxton, Scott, Yednock, Ted, Shaler, Thomas, Johnston, Jennifer A.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149353/

id	pubmed-4149353
recordtype	oai_dc
spelling	pubmed-41493532014-09-03 Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms Riley, Brigit E. Gardai, Shyra J. Emig-Agius, Dorothea Bessarabova, Marina Ivliev, Alexander E. Schüle, Birgit Alexander, Jeff Wallace, William Halliday, Glenda M. Langston, J. William Braxton, Scott Yednock, Ted Shaler, Thomas Johnston, Jennifer A. Research Article 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. Public Library of Science 2014-08-29 /pmc/articles/PMC4149353/ /pubmed/25170892 http://dx.doi.org/10.1371/journal.pone.0102909 Text en © 2014 Riley et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Riley, Brigit E. Gardai, Shyra J. Emig-Agius, Dorothea Bessarabova, Marina Ivliev, Alexander E. Schüle, Birgit Alexander, Jeff Wallace, William Halliday, Glenda M. Langston, J. William Braxton, Scott Yednock, Ted Shaler, Thomas Johnston, Jennifer A.
spellingShingle	Riley, Brigit E. Gardai, Shyra J. Emig-Agius, Dorothea Bessarabova, Marina Ivliev, Alexander E. Schüle, Birgit Alexander, Jeff Wallace, William Halliday, Glenda M. Langston, J. William Braxton, Scott Yednock, Ted Shaler, Thomas Johnston, Jennifer A. Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms
author_facet	Riley, Brigit E. Gardai, Shyra J. Emig-Agius, Dorothea Bessarabova, Marina Ivliev, Alexander E. Schüle, Birgit Alexander, Jeff Wallace, William Halliday, Glenda M. Langston, J. William Braxton, Scott Yednock, Ted Shaler, Thomas Johnston, Jennifer A.
author_sort	Riley, Brigit E.
title	Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms
title_short	Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms
title_full	Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms
title_fullStr	Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms
title_full_unstemmed	Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms
title_sort	systems-based analyses of brain regions functionally impacted in parkinson's disease reveals underlying causal mechanisms
description	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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149353/
_version_	1613129315901243392

Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms

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