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靶向 p53 治疗神经炎症:缺血性脑卒中的新治疗策略。

Targeting p53 for neuroinflammation: New therapeutic strategies in ischemic stroke.

机构信息

Department of Neurology, Lanzhou University Second Hospital, Lanzhou, China.

NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China.

出版信息

J Neurosci Res. 2023 Sep;101(9):1393-1408. doi: 10.1002/jnr.25200. Epub 2023 May 8.

Abstract

Ischemic stroke (IS) is characterized by high incidence, high recurrence, and high mortality and places a heavy burden on society and families. The pathological mechanisms of IS are complex, among which secondary neurological impairment mediated by neuroinflammation is considered to be the main factor in cerebral ischemic injury. At present, there is still a lack of specific therapies to treat neuroinflammation. The tumor suppressor protein p53 has long been regarded as a key substance in the regulation of the cell cycle and apoptosis in the past. Recently, studies have found that p53 also plays an important role in neuroinflammatory diseases, such as IS. Therefore, p53 may be a crucial target for the regulation of the neuroinflammatory response. Here, we provide a comprehensive review of the potential of targeting p53 in the treatment of neuroinflammation after IS. We describe the function of p53, the major immune cells involved in neuroinflammation, and the role of p53 in inflammatory responses mediated by these cells. Finally, we summarize the therapeutic strategies of targeting p53 in regulating the neuroinflammatory response after IS to provide new directions and ideas for the treatment of ischemic brain injury.

摘要

缺血性脑卒中(IS)具有发病率高、复发率高、死亡率高的特点,给社会和家庭带来了沉重的负担。IS 的病理机制复杂,其中神经炎症介导的继发性神经损伤被认为是脑缺血损伤的主要因素。目前,仍然缺乏特异性治疗神经炎症的方法。肿瘤抑制蛋白 p53 长期以来被认为是过去细胞周期和细胞凋亡调节的关键物质。最近的研究发现,p53 在神经炎症性疾病(如 IS)中也起着重要作用。因此,p53 可能是调节神经炎症反应的关键靶点。在这里,我们全面综述了靶向 p53 治疗 IS 后神经炎症的潜力。我们描述了 p53 的功能、参与神经炎症的主要免疫细胞以及 p53 在这些细胞介导的炎症反应中的作用。最后,我们总结了靶向 p53 调节 IS 后神经炎症反应的治疗策略,为缺血性脑损伤的治疗提供了新的方向和思路。

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