Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains
| Autor: | Haenig, C., Atias, N., Taylor, A.K., Mazza, A., Schaefer, M.H., Russ, J., Riechers, S.P., Jain, S., Coughlin, M., Fontaine, J.F., Freibaum, B.D., Brusendorf, L., Zenkner, M., Porras, P., Stroedicke, M., Schnoegl, S., Arnsburg, K., Boeddrich, A., Pigazzini, L., Heutink, P., Taylor, J.P., Kirstein, J., Andrade-Navarro, M.A., Sharan, R., Wanker, E.E. |
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| Rok vydání: | 2019 |
| Předmět: |
methods [Protein Interaction Mapping]
methods [Brain Mapping] Brain Mapping Protein Aggregates genetics [Neurodegenerative Diseases] Protein Interaction Mapping Brain Humans Neurodegenerative Diseases ddc:610 physiopathology [Brain] Function and Dysfunction of the Nervous System genetics [Protein Aggregates] |
| Zdroj: | Cell reports 32(7), 108050-(2020). doi:10.1016/j.celrep.2020.108050 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2020.108050 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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