Annexin A5 in Ischemic Stroke: Molecular Mechanisms and Translational Therapy Strategies

Previous research has identified externalized phosphatidylserine (PS) as an "eat me" signal in apoptosis regulation. Targeting PS thus represents a promising therapeutic approach. Annexin A5, known for its high affinity for PS, has traditionally been used as a FITC-labeled probe for detecting apoptosis. Recent studies have demonstrated that Annexin A5 can cross the blood-brain barrier and selectively bind to PS-exposed injured tissues, exerting multiple protective effects, such as anticoagulant, anti-inflammatory, and anti-apoptotic actions. Furthermore, emerging evidence suggests that Annexin A5 holds potential for molecular imaging of the ischemic penumbra and for the development of lesion-targeted drug delivery systems. In summary, Annexin A5 has garnered increasing attention for its neuroprotective properties and therapeutic potential. Ischemic stroke is one of the leading causes of disability and mortality worldwide. Ischemic stroke management still requires effective neuroprotective agents and innovative imaging strategies to improve clinical outcomes. This article provides a comprehensive analysis of protective mechanisms and translational applicability of Annexin A5 in ischemic stroke therapy, offering novel insights for the development of next-generation multi-target cerebrovascular interventions.