Multiple BACE1 inhibitors abnormally increase the BACE1 protein level in neurons by prolonging its half-life.

DISCUSSION: Elevation of BACE1 by 7 of 8 BACE1 inhibitors raises new concerns about advancing such β-secretase inhibitors for AD. Chronic elevation could lead to intermittently uninhibited BACE1 when orally dosed inhibitors reach trough levels, abnormally increasing substrate processing. Compounds such as roburic acid that lower Aβ by dissociating β/γ secretase complexes are better candidates because they neither inhibit β- and γ-secretase nor increase BACE1 levels. PMID: 31416794 [PubMed - as supplied by publisher]
Source: The Journal of Alzheimers Association - Category: Psychiatry Tags: Alzheimers Dement Source Type: research