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| Status |
Public on Sep 01, 2014 |
| Title |
Systems-based analyses of brain regions functionally impacted in Parkinson's disease reveals underlying causal mechanisms |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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
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| Contributor(s) |
Riley BE, Gardai SJ, Emig-Agius D, Bessarabova M, Ivliev AE, Schule B, Alexander J, Wallace W, Halliday GM, Langston JW, Braxton S, Yednock T, Shaler T, Johnston JA |
| Citation(s) |
25170892 |
| Submission date |
Jan 22, 2014 |
| Last update date |
May 05, 2015 |
| Contact name |
Brigit Erin Riley |
| E-mail(s) |
brigitriley@gmail.com
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| Organization name |
Elan Pharmaceuticals
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| Street address |
180 Oyster Point Blvd.
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| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
USA |
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| Platforms (1) |
| GPL17047 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [HuGene10stv1_Hs_ENTREZG_15.0.0] |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA236096 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54282_RAW.tar |
153.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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