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| Item Type: | Article |
|---|---|
| Title: | Interactome mapping provides a network of neurodegenerative disease proteins and uncovers widespread protein aggregation in affected brains |
| Creators: |
Haenig, C.  ORCID: https://orcid.org/0000-0003-1973-7646, Atias, N., Taylor, A.K., Mazza, A., Schaefer, M.H., Russ, J. ORCID: https://orcid.org/0000-0001-6550-761X, Riechers, S.P. ORCID: https://orcid.org/0000-0001-6933-9174, Jain, S., Coughlin, M., Fontaine, J.F. ORCID: https://orcid.org/0000-0002-1101-4091, Freibaum, B.D., Brusendorf, L., Zenkner, M., Porras, P. ORCID: https://orcid.org/0000-0002-8429-8793, Stroedicke, M., Schnoegl, S., Arnsburg, K., Boeddrich, A. ORCID: https://orcid.org/0000-0001-9118-050X, Pigazzini, L., Heutink, P., Taylor, J.P., Kirstein, J. ORCID: https://orcid.org/0000-0003-4990-2497, Andrade-Navarro, M.A., Sharan, R. and Wanker, E.E. ORCID: https://orcid.org/0000-0001-8072-1630
|
| Abstract: | Interactome maps are valuable resources to elucidate protein function and disease mechanisms. Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions. This network reveals interconnectivity across diseases and links many known ND-causing proteins, such as α-synuclein, TDP-43, and ATXN1, to a host of proteins previously unrelated to NDs. It facilitates the identification of interacting proteins that significantly influence mutant TDP-43 and HTT toxicity in transgenic flies, as well as of ARF-GEP(100) that controls misfolding and aggregation of multiple ND-causing proteins in experimental model systems. Furthermore, it enables the prediction of ND-specific subnetworks and the identification of proteins, such as ATXN1 and MKL1, that are abnormally aggregated in postmortem brains of Alzheimer's disease patients, suggesting widespread protein aggregation in NDs. |
| Keywords: | Neurodegenerative Diseases, Protein-Protein Interactions, Protein Aggregation, Disease Network Modules, Aggregation Modulators, Yeast-Two-Hybrid, Disease-Causing Proteins, PPI Validation, TDP-43, ARF-GEP(100) |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 32 |
| Number: | 7 |
| Page Range: | 108050 |
| Date: | 18 August 2020 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2020.108050 |
| PubMed: | View item in PubMed |
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