Aryloxypropanolamine targets amyloid aggregates and reverses Alzheimer-like phenotypes in Alzheimer mouse models.

ABSTRACT:

Background

Aggregated amyloid-β (Aβ) is considered a pathogenic initiator of Alzheimer's disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aβ is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aβ aggregates.

Methods

The dissociative activity of aryloxypropanolamine derivatives against Aβ aggregates were evaluated throu

SUBMITTER: Lee HY 

PROVIDER: S-EPMC9706920 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature