Transcriptomics

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


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. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene 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 alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression. Substantia Nigra (3 normal, 3 PD), Striatum (6 normal, 6 PD), Cortex (5 normal, 5 PD), Cortex non-PD neurodegeneration (2 normal, 3 DLB). Note Sample X201264 was used both for Cortex normal and for Cortex nonPD normal

ORGANISM(S): Homo sapiens  

SUBMITTER: Jeff Alexander   Glenda M Halliday  William Wallace  Brigit Erin Riley  Ted Yednock  Brigit E Riley  Shyra J Gardai  Jennifer A Johnston  J W Langston  Scott Braxton  Marina Bessarabova  Thomas Shaler  Alexander E Ivliev  Dorothea Emig-Agius  Birgit Schule 

PROVIDER: E-GEOD-54282 | ArrayExpress | 2014-09-01

SECONDARY ACCESSION(S): GSE54282PRJNA236096

REPOSITORIES: GEO, ArrayExpress

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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 experiment  ...[more]

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