ArticleLife science alliance2018
BACE2 distribution in major brain cell types and identification of novel substrates.
Article in Life science alliance, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 71 citations in OpenAlex.
- Elenbecestat and Compound 89 Potently Inhibit BACE1 but Not BACE2 When Subchronically Dosed in Non-Human Primates.Proteomics · 2026Article
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- Modulating Cerebrospinal Fluid Composition in Neurodegenerative Processes: Modern Drug Delivery and Clearance Strategies.International journal of molecular sciences · 2025Review
- Expression and function of β-site amyloid precursor protein-cleaving enzyme 2 in vascular endothelium.American journal of physiology. Heart and circulatory physiology · 2025Article
- Multicolor, Cell-Impermeable, and High Affinity BACE1 Inhibitor Probes Enable Superior Endogenous Staining and Imaging of Single Molecules.Journal of medicinal chemistry · 2024Article
- The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.The Journal of clinical investigation · 2024Article
- BACE2 deficiency impairs expression and function of endothelial nitric oxide synthase in brain endothelial cells.Journal of neurochemistry · 2023Article
- New Highly Selective BACE1 Inhibitors and Their Effects on Dendritic Spine Density In Vivo.International journal of molecular sciences · 2023Article
- The Roles of the Amyloid Beta Monomers in Physiological and Pathological Conditions.Biomedicines · 2023Review
- 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
- The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes.Cellular and molecular life sciences : CMLS · 2022Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Genetic Mapping of APP and Amyloid-β Biology Modulation by Trisomy 21.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Amylin and Secretases in the Pathology and Treatment of Alzheimer's Disease.Biomolecules · 2022Review
- AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.EMBO molecular medicine · 2022Article
- BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids.Cell death discovery · 2022Article
- Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome.PloS one · 2022Article
- Amyloid Beta Dynamics in Biological Fluids-Therapeutic Impact.Journal of clinical medicine · 2021Review
- The case for low-level BACE1 inhibition for the prevention of Alzheimer disease.Nature reviews. Neurology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-Site APP-cleaving enzyme 1 (BACE1) inhibition is considered one of the most promising therapeutic strategies for Alzheimer's disease, but current BACE1 inhibitors also block BACE2. As the localization and function of BACE2 in the brain remain unknown, it is difficult to predict whether relevant side effects can be caused by off-target inhibition of BACE2 and whether it is important to generate BACE1-specific inhibitors. Here, we show that BACE2 is expressed in discrete subsets of neurons and glia throughout the adult mouse brain. We uncover four new substrates processed by BACE2 in cultured glia: vascular cell adhesion molecule 1, delta and notch-like epidermal growth factor-related receptor, fibroblast growth factor receptor 1, and plexin domain containing 2. Although these substrates were not prominently cleaved by BACE2 in healthy adult mice, proinflammatory TNF induced a drastic increase in BACE2-mediated shedding of vascular cell adhesion molecule 1 in CSF. Thus, although under steady-state conditions the effect of BACE2 cross-inhibition by BACE1-directed inhibitors is rather subtle, it is important to consider that side effects might become apparent under physiopathological conditions that induce TNF expression.
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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.