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Interactome mapping provides a network of neurodegenerative disease proteins and uncovers widespread protein aggregation in affected brains

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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 Name:Haenig, C. and Atias, N. and Taylor, A.K. and Mazza, A. and Schaefer, M.H. and Russ, J. and Riechers, S.P. and Jain, S. and Coughlin, M. and Fontaine, J.F. and Freibaum, B.D. and Brusendorf, L. and Zenkner, M. and Porras, P. and Stroedicke, M. and Schnoegl, S. and Arnsburg, K. and Boeddrich, A. and Pigazzini, L. and Heutink, P. and Taylor, J.P. and Kirstein, J. and Andrade-Navarro, M.A. and Sharan, R. and Wanker, E.E.
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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