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Hosp, F.* ; Vossfeldt, H.* ; Heinig, M.* ; Vasiljevic, D.* ; Arumughan, A.* ; Wyler, E.* ; Genetic and Environmental Risk for Alzheimer's Disease (GERAD1) Consortium (Klopp, N.* ; Wichmann, H.-E.*) ; Landthaler, M.* ; Hubner, N.* ; Wanker, E.E.* ; Lannfelt, L.* ; Ingelsson, M.* ; Lalowski, M.* ; Voigt, A.*

Quantitative interaction proteomics of neurodegenerative disease proteins.

Cell Rep. 11, 1134-1146 (2015)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 11, Heft: 7, Seiten: 1134-1146 Artikelnummer: , Supplement: ,
Verlag Cell Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)