BACE2 beyond β‐processing of APP, its neuroprotective role in cerebrovascular endothelium

In Alzheimer's disease, an imbalance between the β-site amyloid precursor protein cleaving enzyme 2 (BACE2) and 1 (BACE1), with a BACE2 decrease and a BACE1 increase of their functions in brain endothelial cells, could lead to failure in soluble non-amyloidogenic APP fragment (sAPPα)-mediated vasoprotective functions and the accumulation of cere brovascular amyloid beta (Aβ) deposits, respectively. This Editorial highlights a study by Katusic et al, who report that BACE2 plays a role in preservation of cerebral vascular endothelial nitric oxide synthase (eNOS) function, thus exerting protective functions mediated by sAPPα through the γ-a minobutyric acid (GABA) type B receptor 1, which enhances the expression of a major transcription factor for eNOS gene expression in endothelial cells, the Krüppel-like factor 2. AbstractSeveral proteases are involved in the proteolytic processing of the amyloid precursor protein (APP) generating the amyloidogenic A β peptide, which can act as the triggering pathological effector of Alzheimer's disease (AD). Among these proteases, the β-site amyloid precursor protein cleaving enzyme 2 (BACE2) is of particular interest because it was first proposed as an alternative β-secretase to its homolog BACE1; however, accumulating evidence suggests that BACE2 acts as a non-amyloidogenic α-secretase and exerts neuroprotective effects. In this issue ofJ Neurochem, Katusic et al. present an interesting article reporting that BACE2 plays a role in...

Source: Journal of Neurochemistry - August 17, 2023 Category: Neuroscience Authors: Javier S áez‐Valero, Rocío Pérez‐González Tags: EDITORIAL Source Type: research