{"title":"BACE2的失活刺激人脑微血管内皮细胞释放内皮素-1。","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":"{\"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}","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}
Inactivation of BACE2 stimulates release of endothelin-1 from human brain microvascular endothelial cells.
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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