ArticleNature communications2017
ER-associated degradation regulates Alzheimer's amyloid pathology and memory function by modulating γ-secretase activity.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 72 citations in OpenAlex.
- RNF185 destabilizes specific membrane proteins that span all ERAD branches.bioRxiv : the preprint server for biology · 2026Article
- Advances in Research on Endoplasmic Reticulum-Associated Degradation Mechanisms in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2026Review
- Membralin Assembles a MAN1B1-VCP Complex to Target Foreign Glycoproteins from the Endoplasmic Reticulum to Lysosomes for Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- The IDO1/AhR-HIF-1α metabolic axis: ARNT competition as a central antagonistic switch in autoimmune pathogenesis.Frontiers in immunology · 2026Review
- Neuro-psycho MMSig: multimodal mechanism enrichment platform for neuropsychiatric disorders.Frontiers in bioinformatics · 2026Article
- Oxidative stress-driven transcriptomic remodeling in human astrocytes reveals network signatures associated with neurodegenerative and cardiovascular processes.Computational and structural biotechnology journal · 2026Article
- Modulation of Ryanodine Receptors on Microglial Ramification, Migration, and Phagocytosis in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2025Article
- A reagent-free, fouling-resistant electrochemical multifunctional peptide sensor for highly sensitive and rapid detection of Alzheimer's disease biomarkers.Materials today. Bio · 2025Article
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Selective clearance of aberrant membrane proteins by TORC1-mediated micro-ER-phagy.Cell reports · 2025Article
- Dynamic Outlier Slicing Allows Broader Exploration of Adaptive Divergence: A Comparison of Individual Genome and Pool-Seq Data Linked to Humic Adaptation in Perch.Molecular ecology · 2025Article
- Targeting endoplasmic reticulum stress-induced CLGN resensitizes hepatocellular carcinoma to apoptosis: paeonol synergistically enhances efficacy by dual inhibition of CLGN and NF-κB.Frontiers in oncology · 2025Article
- Article
- Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.Nature communications · 2024Article
- The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.Journal of biomedical science · 2024Review
- Membralin is required for maize development and defines a branch of the endoplasmic reticulum-associated degradation pathway in plants.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells.Journal of Zhejiang University. Science. B · 2024Review
- SNX17 Mediates Dendritic Spine Maturation via p140Cap.Molecular neurobiology · 2024Article
- Identification of the changes in the platelet proteomic profile of elderly individuals.Frontiers in cardiovascular medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
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 neuronal degeneration. In a mouse AD model, downregulating membralin results in β-amyloid pathology, neuronal death, and exacerbates synaptic/memory deficits. Our results identify membralin as an ERAD component and demonstrate a critical role for ERAD in AD pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.