Phosphatidylserine: A Novel Target for Ischemic Stroke Treatment

Over the past 40 years, research has heavily emphasized stroke treatments that directly target ischemic cascades after stroke onset. Much attention has focused on studying neuroprotective drugs targeting one aspect of the ischemic cascade. However, the single-target therapeutic approach resulted in minimal clinical benefit and poor outcomes in patients. Considering the ischemic cascade is a multifaceted and complex pathophysiological process with many interrelated pathways, the spotlight is now shifting towards the development of neuroprotective drugs that affect multiple aspects of the ischemic cascade. Phosphatidylserine (PS), known as the "eat-me" signal, is a promising candidate. PS is involved in many pathophysiological changes in the central nervous system after stroke onset, including apoptosis, inflammation, coagulation, and neuronal regeneration. Moreover, PS might also exert various roles in different phases after stroke onset. In this review, we describe the synthesis, regulation, and function of PS under physiological conditions. Furthermore, we also summarize the different roles of PS after stroke onset. More importantly, we also discuss several treatment strategies that target PS. We aim to advocate a novel stroke care strategy by targeting PS through a translational perspective.