ArticleBiological psychiatry2018
Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibition Impairs Synaptic Plasticity via Seizure Protein 6.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review.Neurochemical research · 2023Pooled it
- Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial.JAMA neurology · 2021Trial
- GalNAc-T13 maintains neurite architecture and memory retention via O-GalNAc glycosylation of seizure protein 6.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SEZ6L2 Loss Disrupts Motor Coordination, Cognitive Function, and Synaptic Connectivity.bioRxiv : the preprint server for biology · 2026Article
- Sez6L2 autoimmunity induces cerebellar ataxia in mice.Journal of neuroinflammation · 2025Article
- Seizure-Related Homolog Protein 6 (SEZ6): Biology and Therapeutic Target in Neuroendocrine Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Regulation of Apoptotic Pathways by MicroRNAs: A Therapeutic Strategy for Alzheimer's Disease.Molecular neurobiology · 2025Review
- Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer's disease.Science advances · 2025Article
- Alleviation of Neurological Disorders by Targeting Neurodegenerative-Associated Enzymes: Natural and Synthetic Molecules.International journal of molecular sciences · 2025Review
- BACE1 at the crossroads of a vicious circle between Alzheimer's disease and diabetes mellitus.Frontiers in dementia · 2025Review
- Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease.PLoS biology · 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
- Article
- Combination strategy employing BACE1 inhibitor and memantine to boost cognitive benefits in Alzheimer's disease therapy.Psychopharmacology · 2024Article
- BACE1 in PV interneuron tunes hippocampal CA1 local circuits and resets priming of fear memory extinction.Molecular psychiatry · 2023Article
- Physiological Roles of β-amyloid in Regulating Synaptic Function: Implications for AD Pathophysiology.Neuroscience bulletin · 2023Review
- New Highly Selective BACE1 Inhibitors and Their Effects on Dendritic Spine Density In Vivo.International journal of molecular sciences · 2023Article
- The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.Molecular neurodegeneration · 2023Article
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBeta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a promising drug target for the treatment of Alzheimer's disease. Prolonged BACE1 inhibition interferes with structural and functional synaptic plasticity in mice, most likely by altering the metabolism of BACE1 substrates. Seizure protein 6 (SEZ6) is predominantly cleaved by BACE1, and Sez6 knockout mice share some phenotypes with BACE1 inhibitor-treated mice. We investigated whether SEZ6 is involved in BACE1 inhibition-induced structural and functional synaptic alterations.
methodsThe function of NB-360, a novel blood-brain barrier penetrant and orally available BACE1 inhibitor, was verified by immunoblotting. In vivo microscopy was applied to monitor the impact of long-term pharmacological BACE1 inhibition on dendritic spines in the cerebral cortex of constitutive and conditional Sez6 knockout mice. Finally, synaptic functions were characterized using electrophysiological field recordings in hippocampal slices.
resultsBACE1 enzymatic activity was strongly suppressed by NB-360. Prolonged NB-360 treatment caused a reversible spine density reduction in wild-type mice, but it did not affect Sez6
conclusionsOur results suggest that SEZ6 plays an important role in maintaining normal dendritic spine dynamics. Furthermore, SEZ6 is involved in BACE1 inhibition-induced structural and functional synaptic alterations.
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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.