ArticleMolecular psychiatry2021
BACE1 controls synaptic function through modulating release of synaptic vesicles.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 40 citations in OpenAlex.
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
- Maternal Immune Activation Leads to Lasting Sex-Specific Changes in Behavior and Hippocampal Morphological and Molecular Features in 12-Month-Old Rat Offspring.International journal of molecular sciences · 2026Article
- Development of a Novel AAV-Mediated microRNA Gene Therapy for Spatial Suppression of BACE1 to Improve Cognitive Function in Alzheimer's Disease Model Mice.Biomolecules · 2026Article
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Defining pain trajectories in juvenile arthritis and associated patient characteristics.Arthritis research & therapy · 2026Article
- Novel Pyrazoline Derivatives as Therapeutic Candidate for Alzheimer's Disease: An Integrated Network Pharmacology and 3D-QSAR Modelling.Bioinformatics and biology insights · 2026Article
- Article
- BACE1 Expression Is Required for Proper Synaptic Vesicle Dynamics in the Hippocampus.Journal of neurochemistry · 2025Article
- Molecular Mechanisms of EDC-Induced Alzheimer's Disease and of Traditional Chinese Medicine Active Substances in Treating AD and Antagonizing EDC-Induced Effects.Neurochemical research · 2025Article
- Neuronal and Glial α7 Nicotinic Acetylcholine Receptors: Role in Alzheimer's Disease Pathophysiology.Life (Basel, Switzerland) · 2025Review
- Gnb5 is a negative regulator of the BACE1-mediated Aβ generation and ameliorates cognitive deficits in a mouse model of Alzheimer's disease.PLoS biology · 2025Article
- A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Multicolor, Cell-Impermeable, and High Affinity BACE1 Inhibitor Probes Enable Superior Endogenous Staining and Imaging of Single Molecules.Journal of medicinal chemistry · 2024Article
- Associations of CSF BACE1 with amyloid pathology, neurodegeneration, and cognition in Alzheimer's disease.Acta neuropathologica · 2024Article
- Review
- BACE1 in PV interneuron tunes hippocampal CA1 local circuits and resets priming of fear memory extinction.Molecular psychiatry · 2023Article
- Morphofunctional Changes in Brain and Peripheral Blood in Adult and Aged Wistar Rats with AlClBiomedicines · 2023Article
- Physiological Roles of β-amyloid in Regulating Synaptic Function: Implications for AD Pathophysiology.Neuroscience bulletin · 2023Review
- Investigation of Potential Drug Targets for Cholesterol Regulation to Treat Alzheimer's Disease.International journal of environmental research and public health · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
BACE1 initiates production of β-amyloid peptides (Aβ), which is associated with cognitive dysfunction in Alzheimer's disease (AD) due to abnormal oligomerization and aggregation. While BACE1 inhibitors show strong reduction in Aβ deposition, they fail to improve cognitive function in patients, largely due to its role in synaptic function. We show that BACE1 is required for optimal release of synaptic vesicles. BACE1 deficiency or inhibition decreases synaptic vesicle docking in the synaptic active zones. Consistently, BACE1-null mice or mice treated with clinically tested BACE1 inhibitors Verubecestat and Lanabecestat exhibit severe reduction in hippocampal LTP and learning behaviors. To counterbalance this synaptic deficit, we discovered that BACE1-null mice treated with positive allosteric modulators (PAMs) of metabotropic glutamate receptor 1 (mGluR1), whose levels were reduced in BACE1-null mice and significantly improved long-term potentiation and cognitive behaviors. Similarly, mice treated with mGluR1 PAM showed significantly mitigated synaptic deficits caused by BACE1 inhibitors. Together, our data suggest that a therapy combining BACE1 inhibitors for reducing amyloid deposition and an mGluR1 PAM for counteracting BACE1-mediated synaptic deficits appears to be an effective approach for treating AD patients.
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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.