Prothrombin

Prothrombin (F2) is a serine protease precursor that generates thrombin upon cleavage, a central mediator of blood coagulation and hemostasis (UniProt: P00734). Thrombin cleaves fibrinogen to fibrin, activates coagulation factors and protein C, and promotes pro-inflammatory cytokine production in endothelial cells. Beyond hemostasis, prothrombin functions in inflammation and wound healing through interactions with negatively charged surfaces and immune signaling pathways.

UniProt documents prothrombin associations with multiple disorders including Factor II deficiency, ischemic stroke, thrombophilia due to thrombin defect, and recurrent pregnancy loss. The coagulation cascade and thrombin signaling intersect with vascular pathology relevant to stroke and thrombotic complications. Prothrombin's role in endothelial inflammation positions it at the interface between hemostasis and inflammatory processes.

Prothrombin is upregulated in Alzheimer's Disease brain tissue compared to age-matched controls (mean log2FC 0.59; Chaparral AD proteomics). This elevation was detected in post-mortem human AD brain across subcellular fractions using quantitative proteomics. The upregulation may reflect increased hemostatic or inflammatory activity in the AD brain microenvironment, potentially linked to vascular dysfunction or neuroinflammation associated with neurodegeneration.