ArticleThe Journal of biological chemistry2012
The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 187 citations in OpenAlex.
- Small Molecule Therapeutics Targeting Amyloid-β in Alzheimer's Disease: Mechanisms, Clinical Progress, and Future Strategies.Experimental neurobiology · 2026Review
- Microglial NCAM1 attenuates ischemic brain injury by inhibiting NF-κB-driven neuroinflammation through IκBα stabilization.Journal of neuroinflammation · 2026Article
- Plasma Proteome Signature for Leukocyte Telomere Length and Its Link to Abdominal Aortic Aneurysm.Journal of cellular and molecular medicine · 2026Article
- 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
- 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
- Mice Mutated in the First Fibronectin Domain of Adhesion Molecule L1 Show Brain Malformations and Behavioral Abnormalities.Biomolecules · 2024Article
- The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.Molecular neurodegeneration · 2023Article
- CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis.International journal of molecular sciences · 2023Review
- Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity.Nature communications · 2022Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Functional Diversity of Neuronal Cell Adhesion and Recognition Molecule L1CAM through Proteolytic Cleavage.Cells · 2022Review
- The metabolism of human soluble amyloid precursor protein isoforms is quantifiable by a stable isotope labeling-tandem mass spectrometry method.Scientific reports · 2022Article
- BACE1: More than just a β-secretase.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- PTPRD and DCC Are Novel BACE1 Substrates Differentially Expressed in Alzheimer's Disease: A Data Mining and Bioinformatics Study.International journal of molecular sciences · 2022Article
- The β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.Molecular neurobiology · 2022Article
- BACE1: A Key Regulator in Alzheimer's Disease Progression and Current Development of its Inhibitors.Current neuropharmacology · 2022Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedGevaer, Kris [corrected to Gevaert, Kris]
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The β-site amyloid precursor protein-cleaving enzyme BACE1 is a prime drug target for Alzheimer disease. However, the function and the physiological substrates of BACE1 remain largely unknown. In this work, we took a quantitative proteomic approach to analyze the secretome of primary neurons after acute BACE1 inhibition, and we identified several novel substrate candidates for BACE1. Many of these molecules are involved in neuronal network formation in the developing nervous system. We selected the adhesion molecules L1 and CHL1, which are crucial for axonal guidance and maintenance of neural circuits, for further validation as BACE1 substrates. Using both genetic BACE1 knock-out and acute pharmacological BACE1 inhibition in mice and cell cultures, we show that L1 and CHL1 are cleaved by BACE1 under physiological conditions. The BACE1 cleavage sites at the membrane-proximal regions of L1 (between Tyr(1086) and Glu(1087)) and CHL1 (between Gln(1061) and Asp(1062)) were determined by mass spectrometry. This work provides molecular insights into the function and the pathways in which BACE1 is involved, and it will help to predict or interpret possible side effects of BACE1 inhibitor drugs in current clinical trials.
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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.