Article (Scientific journals)
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Haenig, Christian; Atias, Nir; Taylor, Alexander K. et al.
2020In Cell Reports, 32 (7), p. 108050
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Keywords :
Brain/physiopathology; Brain Mapping/methods; Humans; Neurodegenerative Diseases/genetics; Protein Aggregates/genetics; Protein Interaction Mapping/methods; ARF-GEP(100); PPI validation; TDP-43; aggregation modulators; disease network modules; disease-causing proteins; neurodegenerative diseases; protein aggregation; protein-protein interactions; yeast-two-hybrid
Abstract :
[en] 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.
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Author, co-author :
Haenig, Christian
Atias, Nir
Taylor, Alexander K.
Mazza, Arnon
Schaefer, Martin H.
Russ, Jenny
Riechers, Sean-Patrick Hermann  ;  Max Delbrück Center for Molecular Medicine, Neuroproteomics, 13125 Berlin, Germany.
Jain, Shushant
Coughlin, Maura
Fontaine, Jean-Fred
Freibaum, Brian D.
Brusendorf, Lydia
Zenkner, Martina
Porras, Pablo
Stroedicke, Martin
Schnoegl, Sigrid
Arnsburg, Kristin
Boeddrich, Annett
Pigazzini, Lucia
Heutink, Peter
Taylor, J. Paul
Kirstein, Janine
Andrade-Navarro, Miguel A.
Sharan, Roded
Wanker, Erich E.
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Title :
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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Journal title :
Cell Reports
Publisher :
Elsevier, Amsterdam, Netherlands
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Peer reviewed :
Peer Reviewed verified by ORBi
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Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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