Regulation of the p53‑mediated ferroptosis signaling pathway in cerebral ischemia stroke (Review)

Stroke is one of the most threatening diseases worldwide, particularly in countries with larger populations; it is associated with high morbidity, mortality and disability rates. As a result, extensive research efforts are being made to address these issues. Stroke can include either hemorrhagic stroke (blood vessel ruptures) or ischemic stroke (blockage of an artery). Whilst the incidence of stroke is higher in the elderly population (≥65), it is also increasing in the younger population. Ischemic stroke accounts for ~85% of all stroke cases. The pathogenesis of cerebral ischemic injury can include inflammation, excitotoxic injury, mitochondrial dysfunction, oxidative stress, ion imbalance and increased vascular permeability. All of the aforementioned processes have been extensively studied, providing insights into the disease. Other clinical consequences observed include brain edema, nerve injury, inflammation, motor deficits and cognitive impairment, which not only cause disabilities obstructing daily life but also increase the mortality rates. Ferroptosis is a type of cell death that is characterized by iron accumulation and increased lipid peroxidation in cells. In particular, ferroptosis has been previously implicated in ischemia-reperfusion injury in the central nervous system. It has also been identified as a mechanism involved in cerebral ischemic injury. The tumor suppressor p53 has been reported to modulate the ferroptotic signaling pathway, which both positively and negatively affects the prognosis of cerebral ischemia injury. The present review summarizes the recent findings on the molecular mechanisms of ferroptosis under the regulation of p53 underlying cerebral ischemia injury. Understanding of the p53/ferroptosis signaling pathway may provide insights into developing methods for improving the diagnosis, treatment and even prevention of stroke.