First Author | Haenig C | Year | 2020 |
Journal | Cell Rep | Volume | 32 |
Issue | 7 | Pages | 108050 |
PubMed ID | 32814053 | Mgi Jnum | J:296126 |
Mgi Id | MGI:6467711 | Doi | 10.1016/j.celrep.2020.108050 |
Citation | Haenig C, et al. (2020) Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell Rep 32(7):108050 |
abstractText | 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 approximately 5,000 human proteins via approximately 30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of approximately 500 ND-related proteins and integration of literature interactions. This network reveals interconnectivity across diseases and links many known ND-causing proteins, such as alpha-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. |