ArticlePLoS genetics2017
A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
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Who cites it
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- Association Between Irisin Level and Cognitive Function: A Systematic Review and Meta-Analysis.Brain and behavior · 2025Pooled it
- Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer's disease: A systematic review and meta-analysis of animal studies.Frontiers in pharmacology · 2023Pooled it
- Isoform Remodeling and Promoter Switching Identify Altered Transcriptional Regulation in Alzheimer's Disease Frontal Cortex.Research square · 2026Article
- Innovative Test Strip-Based Colorimetric Sensors Integrated With Affinity Chromatography: Acetylcholinesterase Inhibitor Screening Breakthrough in Lycium Barbarum Leaves.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- High intensity 40 Hz flicker improves amyloid pathology and cognition with autophagy in 3xTg mice.iScience · 2026Article
- Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.Nature aging · 2026Article
- Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review).International journal of molecular medicine · 2026Review
- Lifestyle strategies and mechanistic implications for slowing neurodegeneration.npj metabolic health and disease · 2026Review
- Development and characterization of endolysosomal trafficking targeting chimera degraders of αJournal of advanced research · 2026Article
- Autophagy activation by the Becn1Brain, behavior, and immunity · 2026Article
- Exploring the Potential of Herbal Compounds as Autophagy Modulators in Alzheimer's Disease: A Comprehensive Review.CNS & neurological disorders drug targets · 2026Review
- Targeting Liquid-Liquid Phase Separation and Autophagy in Alzheimer's Disease: Insights into Molecular Mechanisms and Therapeutic Potential.Neurochemical research · 2025Review
- The Role and Therapeutic Potential of the cGAS-STING Signaling Pathway in Alzheimer's Disease.Brain and behavior · 2025Review
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Exercise-driven cellular autophagy: A bridge to systematic wellness.Journal of advanced research · 2025Review
- Recruitment of Atg1 to the phagophore by Atg8 orchestrates autophagy machineries.Nature structural & molecular biology · 2025Article
- Anticancer drug development against ribosome synthesis and the nucleolus.Biochemical Society transactions · 2025Article
- Autophagy and Cellular Senescence in Alzheimer's Disease: Key Drivers of Neurodegeneration.CNS neuroscience & therapeutics · 2025Review
- C5a-Induced Autophagy Dysfunction Promotes Choroidal Neovascularization Through the ROS-Inflammatory Pathway.Investigative ophthalmology & visual science · 2025Article
- Antioxidant, Anti-Inflammatory, and Antiapoptotic Effects ofPlants (Basel, Switzerland) · 2025Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid β (Aβ) peptides. Yet the role of autophagy in Aβ production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aβ clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain. Becn1F121A-mediated autophagy hyperactivation significantly decreases amyloid accumulation, prevents cognitive decline, and restores survival in AD mouse models. Using an immunoisolation method, we found biochemically that Aβ oligomers are autophagic substrates and sequestered inside autophagosomes in the brain of autophagy-hyperactive AD mice. In addition to genetic activation of autophagy by Becn1 gain-of-function, we also found that ML246, a small-molecule autophagy inducer, as well as voluntary exercise, a physiological autophagy inducer, exert similar Becn1-dependent protective effects on Aβ removal and memory in AD mice. Taken together, these results demonstrate that genetically disrupting BECN1-BCL2 binding hyperactivates autophagy in vivo, which sequestrates amyloid oligomers and prevents AD progression. The study establishes new approaches to activate autophagy in the brain, and reveals the important function of Becn1-mediated autophagy hyperactivation in the prevention of AD.
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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.