ArticleMolecular neurodegeneration2012
Identification of BACE2 as an avid ß-amyloid-degrading protease.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Effects of BACE2 polymorphisms on verbal memory in the general population.European archives of psychiatry and clinical neuroscience · 2026Article
- Multiomics and proteomic insights into Alzheimer's disease biology in Down syndrome.Expert review of neurotherapeutics · 2026Review
- Expression and function of β-site amyloid precursor protein-cleaving enzyme 2 in vascular endothelium.American journal of physiology. Heart and circulatory physiology · 2025Article
- It's good to know what to BACE the specificity of your inhibitors on.The Journal of clinical investigation · 2024Article
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- BACE2 deficiency impairs expression and function of endothelial nitric oxide synthase in brain endothelial cells.Journal of neurochemistry · 2023Article
- Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.Communications biology · 2023Article
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- BACE2: A Promising Neuroprotective Candidate for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- 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
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids.Cell death discovery · 2022Article
- Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.Cellular and molecular life sciences : CMLS · 2022Review
- Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome.PloS one · 2022Article
- Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.Molecular psychiatry · 2021Article
- A ß-Secretase Modulator Decreases Tau Pathology and Preserves Short-Term Memory in a Mouse Model of Neurofibrillary Degeneration.Frontiers in pharmacology · 2021Article
- Advances in Drug Therapy for Alzheimer's Disease.Current medical science · 2020Review
- Common BACE2 Polymorphisms are Associated with Altered Risk for Alzheimer's Disease and CSF Amyloid Biomarkers in APOE ε4 Non-Carriers.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProteases that degrade the amyloid ß-protein (Aß) have emerged as key players in the etiology and potential treatment of Alzheimer's disease (AD), but it is unlikely that all such proteases have been identified. To discover new Aß-degrading proteases (AßDPs), we conducted an unbiased, genome-scale, functional cDNA screen designed to identify proteases capable of lowering net Aß levels produced by cells, which were subsequently characterized for Aß-degrading activity using an array of downstream assays.
resultsThe top hit emerging from the screen was ß-site amyloid precursor protein-cleaving enzyme 2 (BACE2), a rather unexpected finding given the well-established role of its close homolog, BACE1, in the production of Aß. BACE2 is known to be capable of lowering Aß levels via non-amyloidogenic processing of APP. However, in vitro, BACE2 was also found to be a particularly avid AßDP, with a catalytic efficiency exceeding all known AßDPs except insulin-degrading enzyme (IDE). BACE1 was also found to degrade Aß, albeit ~150-fold less efficiently than BACE2. Aß is cleaved by BACE2 at three peptide bonds-Phe19-Phe20, Phe20-Ala21, and Leu34-Met35--with the latter cleavage site being the initial and principal one. BACE2 overexpression in cultured cells was found to lower net Aß levels to a greater extent than multiple, well-established AßDPs, including neprilysin (NEP) and endothelin-converting enzyme-1 (ECE1), while showing comparable effectiveness to IDE.
conclusionsThis study identifies a new functional role for BACE2 as a potent AßDP. Based on its high catalytic efficiency, its ability to degrade Aß intracellularly, and other characteristics, BACE2 represents a particulary strong therapeutic candidate for the treatment or prevention of AD.
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