Systems-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. 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 ma

SUBMITTER: Riley BE 

PROVIDER: S-EPMC4149353 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature