Platelet-Derived Transforming Growth Factor-β1: A New Hope for Cerebral Malaria Treatment.

Abstract

Cerebral malaria (CM), a fatal neurological complication arising from Plasmodium falciparum (P. falciparum) infection, remains a significant global health challenge due to the inadequacy of current drugs and vaccines. Consequently, novel therapeutic strategies for CM are urgently needed. Recent research identifies platelets as pivotal in CM pathogenesis, significantly contributing to immunopathological damage and vascular blockage. Platelet-derived transforming growth factor (TGF)-β1 induces apoptosis in endothelial cells, fostering microangiopathy and potentially compromising blood-brain barrier integrity, thus provoking brain edema and inflammation. Notably, TGF-β1 concentrations vary markedly between systemic and local levels, with reduced TGF-β1 levels in mouse/human tissue and peripheral circulation correlating with CM severity. The primary regulatory mechanism involves isolated platelets interacting with infected red blood cells and brain endothelium, elevating local TGF-β1 production, and possibly harming brain endothelial cells. Future CM prevention or treatment strategies should focus on targeting TGF-β1, with an emphasis on brain-targeted drug delivery methods. Exosomes, as natural drug carriers, are extensively utilized for brain-specific delivery. Exosomes loaded with TGF-β1 antibodies, which were surface to enhancing brain-targeting ability, offer a promising therapeutic approach for CM.