The ERK signaling pathway in cerebral ischemic stroke: Mechanism and therapeutic significance

Cerebral ischemic stroke (CIS) represents a leading global cause of mortality and long-term disability, posing a significant public health challenge. The pathogenesis of CIS is complex, and effective therapies remain limited. Therefore, elucidating the underlying neurobiological mechanisms of CIS and exploring novel therapeutic strategies are essential. Extracellular signal-regulated kinase (ERK) has emerged as a critical regulator in CIS pathogenesis, playing pivotal roles in cellular processes such as growth, proliferation, differentiation, and signal transduction, while also demonstrating substantial neuroprotective potential. Targeted modulation of ERK signaling holds promise for mitigating multiple pathological cascades in CIS, including endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, apoptosis, excitotoxicity, autophagy, and neuroinflammation, while potentially promoting neural regeneration. Consequently, ERK represents an attractive potential therapeutic target for alleviating CIS. This review first delineates the structure, function, and activation of the ERK pathway. Subsequently, it summarizes current understandings of CIS pathogenesis and critically examines the involvement of ERK signaling in CIS pathophysiology. Finally, the review discusses the mechanistic basis and therapeutic potential of targeting the ERK pathway to ameliorate CIS, providing a scientific rationale for further investigation of ERK as a therapeutic target.