{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhu B"],"funding":["NICHD NIH HHS","NIA NIH HHS","NINDS NIH HHS"],"pagination":["1472"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5684335"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(1)"],"pubmed_abstract":["Endoplasmic-reticulum-associated degradation (ERAD) is an important protein quality control system which maintains protein homeostasis. Constituents of the ERAD complex and its role in neurodegeneration are not yet fully understood. Here, using proteomic and FRET analyses, we demonstrate that the ER protein membralin is an ERAD component, which mediates degradation of ER luminal and membrane substrates. Interestingly, we identify nicastrin, a key component of the γ-secretase complex, as a membralin binding protein and membralin-associated ERAD substrate. We demonstrate a reduction of membralin mRNA and protein levels in Alzheimer's disease (AD) brain, the latter of which inversely correlates with nicastrin abundance. Furthermore, membralin deficiency enhances γ-secretase activity and neuro"],"journal":["Nature communications"],"pubmed_title":["ER-associated degradation regulates Alzheimer's amyloid pathology and memory function by modulating γ-secretase activity."],"pmcid":["PMC5684335"],"funding_grant_id":["R01 NS046673","R01 AG038710","R01 HD074961","R21 AG048519","R01 AG044420","R01 AG021173"],"pubmed_authors":["Pomeroy K","Li X","Jiang L","Huang T","Zhang D","Zhong Y","Zhu B","Liu T","Masliah E","Xu H","Zhao Y","Campos A"],"additional_accession":[]},"is_claimable":false,"name":"ER-associated degradation regulates Alzheimer's amyloid pathology and memory function by modulating γ-secretase activity.","description":"Endoplasmic-reticulum-associated degradation (ERAD) is an important protein quality control system which maintains protein homeostasis. Constituents of the ERAD complex and its role in neurodegeneration are not yet fully understood. Here, using proteomic and FRET analyses, we demonstrate that the ER protein membralin is an ERAD component, which mediates degradation of ER luminal and membrane substrates. Interestingly, we identify nicastrin, a key component of the γ-secretase complex, as a membralin binding protein and membralin-associated ERAD substrate. We demonstrate a reduction of membralin mRNA and protein levels in Alzheimer's disease (AD) brain, the latter of which inversely correlates with nicastrin abundance. Furthermore, membralin deficiency enhances γ-secretase activity and neuro","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Nov","modification":"2026-04-16T09:30:49.171Z","creation":"2019-03-27T03:01:47Z"},"accession":"S-EPMC5684335","cross_references":{"pubmed":["29133892"],"doi":["10.1038/s41467-017-01799-4"]}}