ArticleNature medicine2013
β-arrestin 2 regulates Aβ generation and γ-secretase activity in Alzheimer's disease.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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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.
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Who cites it
109 citing papers in PubMed, 175 citations in OpenAlex.
- Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS.Annals of neurology · 2023Trial
- Article
- Discovery of Small Molecule Ligands Targeting Orphan G Protein-Coupled Receptors GPR3, GPR6, and GPR12.Journal of medicinal chemistry · 2026Review
- Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid-β Production and Cognitive Dysfunctions in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GPR3 Ligands Discovered through Combined Virtual and Conformational Biosensor-Based Screening.Journal of the American Chemical Society · 2026Article
- The GPCR Connection: Linking Alzheimer's Disease and Glioblastoma.Journal of cellular and molecular medicine · 2026Review
- Galanin Receptors: G Protein-Dependent Signaling and Beyond.Biomolecules · 2026Review
- The clinical implication of β-arrestins-mediated signaling in memory and cognition.Molecular and cellular biochemistry · 2025Review
- Age-related decline in protein turnover highlights cystatin C dysfunction and links proteostasis collapse to neuroinflammation in the murine cortex.Biogerontology · 2025Article
- The PKCι-β-arrestin2 axis disrupts SORLA retrograde trafficking, driving its degradation and amyloid pathology in Alzheimer's disease.Molecular neurodegeneration · 2025Article
- IGF1R/ARRB1 Mediated Regulation of ERK and cAMP Pathways in Response to Aβ Unfolds Novel Therapeutic Avenue in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Implication of Central βArchiv der Pharmazie · 2025Review
- Whole-genome bisulfite sequencing of cell-free DNA unveils age-dependent and ALS-associated methylation alterations.Cell & bioscience · 2025Article
- Review
- Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on β-arrestin2 expression and molecular markers of neural injury.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- New precision medicine avenues to the prevention of Alzheimer's disease from insights into the structure and function of γ-secretases.The EMBO journal · 2024Review
- The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases.Experimental & molecular medicine · 2024Review
- Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis.Nature communications · 2024Article
- Investigation of Potential Drug Targets Involved in Inflammation Contributing to Alzheimer's Disease Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Exploring orphan GPCRs in neurodegenerative diseases.Frontiers in pharmacology · 2024Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-arrestins are associated with numerous aspects of G protein-coupled receptor (GPCR) signaling and regulation and accordingly influence diverse physiological and pathophysiological processes. Here we report that β-arrestin 2 expression is elevated in two independent cohorts of individuals with Alzheimer's disease. Overexpression of β-arrestin 2 leads to an increase in amyloid-β (Aβ) peptide generation, whereas genetic silencing of Arrb2 (encoding β-arrestin 2) reduces generation of Aβ in cell cultures and in Arrb2(-/-) mice. Moreover, in a transgenic mouse model of Alzheimer's disease, genetic deletion of Arrb2 leads to a reduction in the production of Aβ(40) and Aβ(42). Two GPCRs implicated previously in Alzheimer's disease (GPR3 and the β(2)-adrenergic receptor) mediate their effects on Aβ generation through interaction with β-arrestin 2. β-arrestin 2 physically associates with the Aph-1a subunit of the γ-secretase complex and redistributes the complex toward detergent-resistant membranes, increasing the catalytic activity of the complex. Collectively, these studies identify β-arrestin 2 as a new therapeutic target for reducing amyloid pathology and GPCR dysfunction in Alzheimer's disease.
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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.