Amyloid-beta-fibrinogen protein-protein interface (Aβ-fibrinogen interface) (Aβ-fibrinogen interface)

The Amyloid-beta-fibrinogen protein-protein interface is a pathological interaction between the amyloid-beta (Aβ) peptide and the blood-clotting protein fibrinogen, primarily involving the Aβ42 isoform and the fibrinogen β-chain or D-domain (Ahn et al., 2010, Neuron [PMID: 20547128]). In Alzheimer's disease (AD), this interaction leads to the formation of abnormal fibrin clots that are structurally altered and highly resistant to degradation by the fibrinolytic enzyme plasmin (Cortes-Canteli et al., 2010, Neuron [PMID: 20547128]). These persistent clots contribute to chronic cerebral hypoperfusion, neuroinflammation, and blood-brain barrier disruption, which accelerate cognitive decline and neurodegeneration (Cortes-Canteli et al., 2012, J Alzheimers Dis [PMID: 22451145]). As a therapeutic target, disrupting this interface aims to restore normal fibrinolysis and improve vascular health in the brain without compromising systemic hemostasis. Experimental compounds like the small molecule RU-505 have demonstrated the ability to bind Aβ and inhibit its interaction with fibrinogen, resulting in reduced vascular amyloid deposition and improved memory in AD mouse models (Cortes-Canteli et al., 2014, Blood [PMID: 24532803]). This target represents a novel approach to AD treatment by focusing on the neurovascular component of the disease.

Other names

Amyloid-beta-fibrinogen interactionAβ-fibrinogen complexAβ-fibrinogen binding siteAmyloid-beta-fibrinogen PPI

Disruption of the protein-protein interaction between amyloid-beta and fibrinogen to prevent the formation of fibrinolysis-resistant clots and mitigate neurovascular damage (Cortes-Canteli et al., 2014, Blood [PMID: 24532803]).