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  • Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Cell reports (2020-08-20)
Christian Haenig, Nir Atias, Alexander K Taylor, Arnon Mazza, Martin H Schaefer, Jenny Russ, Sean-Patrick Riechers, Shushant Jain, Maura Coughlin, Jean-Fred Fontaine, Brian D Freibaum, Lydia Brusendorf, Martina Zenkner, Pablo Porras, Martin Stroedicke, Sigrid Schnoegl, Kristin Arnsburg, Annett Boeddrich, Lucia Pigazzini, Peter Heutink, J Paul Taylor, Janine Kirstein, Miguel A Andrade-Navarro, Roded Sharan, Erich E Wanker
RESUMEN

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-GEP100 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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