期刊
CELL REPORTS
卷 11, 期 7, 页码 1134-1146出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.04.030
关键词
-
类别
资金
- NGNF-plus network NeuroNet (BMBF)
- Cross-Program Initiative Personalized Medicine (iMed) of the Helmholtz Association
- Alzheimers Research UK [ARUK-PG2014-1, ART-PG2008-3, ARUK-NCG2014A-1, ARUK-PG2014-2] Funding Source: researchfish
- Alzheimer's Society [167] Funding Source: researchfish
- Medical Research Council [MR/K013041/1, MR/L010305/1, MR/L023784/2, MC_U123192748, MR/L501517/1, G0800509, MR/L501529/1, MC_U123160651, G0902227] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10033] Funding Source: researchfish
- MRC [G0902227, G0800509, MR/K013041/1, MC_U123160651, MC_U123192748, MR/L023784/2] Funding Source: UKRI
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据