Bromo-protopine, a novel protopine derivative, alleviates tau pathology by activating chaperone-mediated autophagy for Alzheimer's disease therapy.

ABSTRACT: Emerging evidence from Alzheimer's disease (AD) patients suggests that reducing tau pathology can restore cognitive and memory loss. To reduce tau pathology, it is critical to find brain-permeable tau-degrading small molecules that are safe and effective. HDAC6 inhibition has long been considered a safe and effective therapy for tau pathology. Recently, we identified protopine as a dibenzazecine alkaloid with anti-HDAC6 and anti-AD activities. In this study, we synthesized and tested novel protopine derivatives for their pharmacological action against AD. Among them, bromo-protopine (PRO-Br) demonstrated a two-fold increase in anti-HDAC6 activity and improved anti-tau activities compared to the parent compound in both in vitro and in vivo AD models. Furthermore, molecular doc

SUBMITTER: Sreenivasmurthy SG 

PROVIDER: S-EPMC9643865 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature