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| Status |
Public on May 12, 2015 |
| Title |
Evidence for immune response, axonal dysfunction and reduced endocytosis preceding Lewy body pathology in the substantia nigra in Parkinson’s disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of Parkinson’s disease (PD). To identify molecular mechanisms underlying neuronal dysfunction and alpha--synuclein pathology in the premotor phase of PD, we investigated the transcriptome of post-mortem substantia nigra (SN) of iLBD, PD donors and age-matched controls with Braak alpha--synuclein stage ranging from 0-6. In Braak alpha--synuclein stages 1 and 2, we observed deregulation of pathways linked to axonal degeneration, unfolded protein response (UPR), immune response and endocytosis, including axonal guidance signaling, protein kinase A signaling, mTOR signaling, EIF2 signaling and clathrin-mediated endocytosis. In Braak stages 3 and 4, we observed a deregulation in pathways involved in protein translation and cell survival, including mTOR and EIF2 signaling. In Braak stages 5 and 6, we observed deregulation of pathways such as dopaminergic signaling, axonal guidance signaling and thrombin signaling. Throughout the progression of PD pathology, we observed a deregulation of mTOR, EIF2 and regulation of eIF4 and p70S6K signaling in the SN. This implicates that molecular mechanisms related to UPR, axonal dysfunction, endocytosis and immune response are an early event in PD pathology, and may hold the key to altering the disease progression in PD.
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| Overall design |
Control Braak α- synuclein Stage 0: 8 samples;α Braak α-synuclein stage 1-2: 5 samples; Braak α-synuclein 3-4 7 samples; Braak α-synuclein stages 5-6 :8 samples
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| Contributor(s) |
Dijkstra AA, Ingrassia AI, de Menezes RX, van Kesteren RE, Rozemuller AM, Heutink P, vandeBerg WJ |
| Citation(s) |
26087293 |
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| Submission date |
Jul 19, 2013 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Anke Akke Dijkstra |
| Organization name |
Vu Medical center
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| Department |
Anatomy and neurosciences
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| Street address |
Van der Boechorststraat 7
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| City |
Amsterdam |
| ZIP/Postal code |
1081 BT |
| Country |
Netherlands |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (28)
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| GSM1192691 |
Control Braak α- synuclein Stage 0 C1SN |
| GSM1192692 |
Control Braak α- synuclein Stage 0 C2SN |
| GSM1192693 |
Control Braak α- synuclein Stage 0 C3SN |
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| Relations |
| BioProject |
PRJNA212736 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49036_RAW.tar |
128.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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