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Omics score: 1008

Quantitative interaction proteomics of neurodegenerative disease proteins.

ABSTRACT: Data from ProteomeXchange, PXD ID: PXD001942. File: 20130829_Orbi6_FaHo_SA_NN_SWEvsEV_Rep3_01.mzml. Published as part of Cell Rep. 2015 May 19;11(7):1134-46 . From the Abstract: {{i}} 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 ... {{/i}}

INSTRUMENT(S): Instrument

ORGANISM(S): Homo_sapiens_viruses, Human_female

DISEASE(S): Not Available

SUBMITTER: Hosp F, et al.

PROVIDER: GPM32320018141 | GPMDB |

REPOSITORIES: GPMDB

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Quantitative interaction proteomics of neurodegenerative disease proteins.

Hosp Fabian F Vossfeldt Hannes H Heinig Matthias M Vasiljevic Djordje D Arumughan Anup A Wyler Emanuel E Landthaler Markus M Hubner Norbert N Wanker Erich E EE Lannfelt Lars L Ingelsson Martin M Lalowski Maciej M Voigt Aaron A Selbach Matthias M

Cell reports 20150507 7

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 degrad ...[more]

PMID: 25959826

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Quantitative interaction proteomics of neurodegenerative disease proteins

Project description: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 Alzheimerâ€™s disease (AD), Huntingtin (HTT) for Huntingtonâ€™s disease, Parkin-2 (PARK-2) for Parkinsonâ€™s disease and Ataxin-1 (ATXN-1) 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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