ArticleThe Journal of biological chemistry2012
Identification of novel γ-secretase-associated proteins in detergent-resistant membranes from brain.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- The compartment-specific interactome of VDAC1 reveals its emerging role beyond mitochondria in breast cancer.Scientific reports · 2026Article
- Identification of highly reliable risk genes for Alzheimer's disease through joint-tissue integrative analysis.Frontiers in aging neuroscience · 2023Article
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- γ-Secretase in Alzheimer's disease.Experimental & molecular medicine · 2022Review
- The Potential of Small Molecules to Modulate the Mitochondria-Endoplasmic Reticulum Interplay in Alzheimer's Disease.Frontiers in cell and developmental biology · 2022Review
- Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer's disease and normal physiology.Frontiers in cell and developmental biology · 2022Review
- VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases.Biomolecules · 2020Review
- Article
- γ-Secretase Partitioning into Lipid Bilayers Remodels Membrane Microdomains after Direct Insertion.Langmuir : the ACS journal of surfaces and colloids · 2020Article
- Contactin-1 Is Required for Peripheral Innervation and Immune Homeostasis Within the Intestinal Mucosa.Frontiers in immunology · 2020Article
- Ubiquitin C-terminal Hydrolase L1 Regulates Lipid Raft-dependent Endocytosis.Experimental neurobiology · 2018Article
- β-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders.Frontiers in pharmacology · 2018Review
- Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases.Neural regeneration research · 2017Review
- Nogo receptor 1 regulates Caspr distribution at axo-glial units in the central nervous system.Scientific reports · 2017Article
- Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels.Alzheimer's research & therapy · 2017Article
- Mitochondrial Proteome Changes Correlating with β-Amyloid Accumulation.Molecular neurobiology · 2017Article
- Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid β-peptide production.Journal of cellular and molecular medicine · 2016Article
- The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.Molecular neurobiology · 2016Review
- Physical and functional interaction between the α- and γ-secretases: A new model of regulated intramembrane proteolysis.The Journal of cell biology · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Alzheimer disease, oligomeric amyloid β-peptide (Aβ) species lead to synapse loss and neuronal death. γ-Secretase, the transmembrane protease complex that mediates the final catalytic step that liberates Aβ from its precursor protein (APP), has a multitude of substrates, and therapeutics aimed at reducing Aβ production should ideally be specific for APP cleavage. It has been shown that APP can be processed in lipid rafts, and γ-secretase-associated proteins can affect Aβ production. Here, we use a biotinylated inhibitor for affinity purification of γ-secretase and associated proteins and mass spectrometry for identification of the purified proteins, and we identify novel γ-secretase-associated proteins in detergent-resistant membranes from brain. Furthermore, we show by small interfering RNA-mediated knockdown of gene expression that a subset of the γ-secretase-associated proteins, in particular voltage-dependent anion channel 1 (VDAC1) and contactin-associated protein 1 (CNTNAP1), reduced Aβ production (Aβ40 and Aβ42) by around 70%, whereas knockdown of presenilin 1, one of the essential γ-secretase complex components, reduced Aβ production by 50%. Importantly, these proteins had a less pronounced effect on Notch processing. We conclude that VDAC1 and CNTNAP1 associate with γ-secretase in detergent-resistant membranes and affect APP processing and suggest that molecules that interfere with this interaction could be of therapeutic use for Alzheimer disease.
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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.