Anti-HK antibody reveals critical roles of a 20-residue HK region for Aβ-induced plasma contact system activation.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia. Vascular abnormalities and neuroinflammation play roles in AD pathogenesis. Plasma contact activation, which leads to fibrin clot formation and bradykinin release, is elevated in many AD patients, likely due to the ability of AD's pathogenic peptide β-amyloid (Aβ) to induce its activation. Since overactivation of this system may be deleterious to AD patients, the development of inhibitors could be beneficial. Here, we show that 3E8, an antibody against a 20-amino acid region in domain 6 of high molecular weight kininogen (HK), inhibits Aβ-induced intrinsic coagulation. Mechanistically, 3E8 inhibits contact system activation by blocking the binding of prekallikrein (PK) and factor XI (FXI) to HK, the

SUBMITTER: Chen ZL 

PROVIDER: S-EPMC9131899 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature