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Under pathological conditions, excessive activation of BACE1 exerts detrimental effects on endothelial function by A\u03b2-dependent and A\u03b2-independent mechanisms. High local concentration of A\u03b2 in the brain blood vessels is responsible for the loss of key vascular protective functions of endothelial cells. More recent studies recognized significant contribution of A\u03b2-independent proteolytic activity of endothelial BACE1 to the pathogenesis of endothelial dysfunction. This review critically evaluates existing evidence supporting the concept that excessive activation of BACE1 expressed in the cerebrovascular endothelium impairs key homeostatic functions of the brain blood vessels. This concept has important therapeutic implications. Indeed, improved understanding of the mechanisms of endothelial dysfunction may help in efforts to develop new approaches to the protection and preservation of healthy cerebrovascular function.<\/jats:p>","DOI":"10.1161\/atvbaha.124.320798","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T09:00:33Z","timestamp":1718269233000},"page":"1737-1747","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Cerebrovascular Endothelial Dysfunction: Role of BACE1"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-7883","authenticated-orcid":true,"given":"Zvonimir S.","family":"Katusic","sequence":"first","affiliation":[{"name":"Departments of Anesthesiology and Perioperative Medicine and Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, 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