Transcriptomics

Dataset Information

37

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 | 2016-08-22

SECONDARY ACCESSION(S): GSE54282PRJNA236096

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications


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]

Similar Datasets

2008-01-01 | GSE8397 | GEO
2012-03-27 | E-GEOD-8397 | ArrayExpress
2014-06-02 | E-GEOD-20164 | ArrayExpress
2011-01-20 | GSE20164 | GEO
2012-03-27 | E-GEOD-20163 | ArrayExpress
2011-01-20 | GSE20163 | GEO
2007-06-14 | GSE7621 | GEO
| GSE49036 | GEO
2015-04-30 | E-GEOD-7621 | ArrayExpress
2014-11-20 | BIOMD0000000559 | BioModels Database