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. 2020 Aug 18;32(7):108050.
doi: 10.1016/j.celrep.2020.108050.

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

Christian Haenig  1 , Nir Atias  2 , Alexander K Taylor  3 , Arnon Mazza  2 , Martin H Schaefer  4 , Jenny Russ  1 , Sean-Patrick Riechers  1 , Shushant Jain  5 , Maura Coughlin  3 , Jean-Fred Fontaine  6 , Brian D Freibaum  3 , Lydia Brusendorf  1 , Martina Zenkner  1 , Pablo Porras  7 , Martin Stroedicke  1 , Sigrid Schnoegl  1 , Kristin Arnsburg  8 , Annett Boeddrich  1 , Lucia Pigazzini  8 , Peter Heutink  5 , J Paul Taylor  9 , Janine Kirstein  8 , Miguel A Andrade-Navarro  6 , Roded Sharan  10 , Erich E Wanker  11
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Free article

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

Christian Haenig et al. Cell Rep. .
Free article

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-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.

Keywords: 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.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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