Aminopyrimidine Class Aggregation Inhibitor Effectively Blocks Aβ-Fibrinogen Interaction and Aβ-Induced Contact System Activation.

ABSTRACT: Accumulating evidence suggests that fibrinogen, a key protein in the coagulation cascade, plays an important role in circulatory dysfunction in Alzheimer's disease (AD). Previous work has shown that the interaction between fibrinogen and β-amyloid (Aβ), a hallmark pathological protein in AD, induces plasmin-resistant abnormal blood clots, delays fibrinolysis, increases inflammation, and aggravates cognitive function in mouse models of AD. Since Aβ oligomers have a much stronger affinity for fibrinogen than Aβ monomers, we tested whether amyloid aggregation inhibitors could block the Aβ-fibrinogen interaction and found that some Aβ aggregation inhibitors showed moderate inhibitory efficacy against this interaction. We then modified a hit compound so that it not only showed a strong inhibito

SUBMITTER: Singh PK 

PROVIDER: S-EPMC5829012 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature