Quantitative interaction proteomics of neurodegenerative disease proteins

Abstract: 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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Cell reports. - 11, 7 (2015) , 1134-1146, ISSN: 2211-1247

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2019
• Urheber: Hosp, Fabian ; Vossfeldt, Hannes ; Heinig, Matthias ; Vasiljevic, Djordje ; Arumughan, Anup ; Wyler, Emanuel ; Landthaler, Markus ; Hubner, Norbert ; Wanker, Erich ; Lannfelt, Lars ; Ingelsson, Martin ; Lalowski, Maciej ; Voigt, Aaron ; Selbach, Matthias
• Beteiligte Personen und Organisationen: Klinik für Psychiatrie und Psychotherapie. Freiburg im Breisgau

Weitere Informationen

• DOI: 10.1016/j.celrep.2015.04.030
• URN: urn:nbn:de:bsz:25-freidok-1260595
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:56 MEZ