{"title":"Inactivation of BACE2 stimulates release of endothelin-1 from human brain microvascular endothelial cells.","authors":"Tongrong He, Zvonimir S Katusic","doi":"10.1177/25424823251371040","DOIUrl":null,"url":null,"abstract":"<p><p>Beta-site amyloid precursor protein cleaving enzyme 2 (BACE2) is one of the most downregulated genes in the brain capillary endothelial cells derived from patients with Alzheimer's disease (AD). Endothelin-1 (ET-1) significantly contributes to the pathogenesis of AD. We hypothesized that loss of BACE2 increases production of ET-1 from human brain microvascular endothelial cells (BMECs). Genetic inactivation of BACE2 in cultured human BMECs significantly upregulated expression and release of ET-1. Mechanistic studies indicated that γ-aminobutyric acid type B receptor subunit 2/transforming growth factor beta 2 signaling pathway mediated the effect of BACE2 inhibition on ET-1 production.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251371040"},"PeriodicalIF":2.8000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365451/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Alzheimer's disease reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/25424823251371040","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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Abstract
Beta-site amyloid precursor protein cleaving enzyme 2 (BACE2) is one of the most downregulated genes in the brain capillary endothelial cells derived from patients with Alzheimer's disease (AD). Endothelin-1 (ET-1) significantly contributes to the pathogenesis of AD. We hypothesized that loss of BACE2 increases production of ET-1 from human brain microvascular endothelial cells (BMECs). Genetic inactivation of BACE2 in cultured human BMECs significantly upregulated expression and release of ET-1. Mechanistic studies indicated that γ-aminobutyric acid type B receptor subunit 2/transforming growth factor beta 2 signaling pathway mediated the effect of BACE2 inhibition on ET-1 production.
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