Molecular mechanisms of programmed cell death and potential targeted pharmacotherapy in ischemic stroke (Review)

• Published in: International journal of molecular medicine Vol. 56; no. 1; pp. 1 - 21
• Main Authors: Duan, Wan-Li, Gu, Li-Hui, Guo, Ai, Wang, Xue-Jie, Ding, Yi-Yue, Zhang, Peng, Zhang, Bao-Gang, Li, Qin, Yang, Li-Xia
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.07.2025; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Autophagy; Biochemistry; Brain damage; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Cell death; Cytochrome; DNA damage; Drug approval; Drug therapy; Edema; Ferroptosis; Homeostasis; Humans; Hypoxia; Ischemia; Ischemic Stroke - drug therapy; Ischemic Stroke - metabolism; Ischemic Stroke - pathology; Kinases; Ligands; Lipids; Liu E; Liu, Timothy; Molecular Targeted Therapy; Pathophysiology; Proteins; Review; Sapropterin dihydrochloride; Stroke; Stroke (Disease); Stroke patients; Thrombolytic drugs; Tissue plasminogen activator; Tissue Plasminogen Activator - therapeutic use; Tissues; Traumatic brain injury; Tumor necrosis factor-TNF; China; PCD; molecular mechanisms; IS; protective drugs; pharmacotherapy
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2025.5544

Stroke poses a threat to the elderly, being the second leading cause of death and the third leading cause of disability worldwide. Ischemic stroke (IS), resulting from arterial occlusion, accounts for ~85% of all strokes. The pathophysiological processes involved in IS are intricate and complex. Currently, tissue plasminogen activator (tPA) is the only Food and Drug Administration‑approved drug for the treatment of IS. However, due to its limited administration window and the risk of symptomatic hemorrhage, tPA is applicable to only ~10% of patients with stroke. Additionally, the reperfusion process associated with thrombolytic therapy can further exacerbate damage to brain tissue. Therefore, a thorough understanding of the molecular mechanisms underlying IS‑induced injury and the identification of potential protective agents is critical for effective IS treatment. Over the past few decades, advances have been made in exploring potential protective drugs for IS. The present review summarizes the specific mechanisms of various forms of programmed cell death (PCD) induced by IS and highlights potential protective drugs targeting different PCD pathways investigated over the last decade. The present review provides a theoretical foundation for basic research and insights for the development of pharmacotherapy for IS.