Inactivation of BACE2 increases endothelin-1 production in brain endothelial cells, suggesting key signaling roles.
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.
No takes yet. Share an insight, caveat, or question.
He et al. (2025) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: