Wang Chenye, Li Sha, Li Qixiu, Xi Haiyan, Li Jiejia, Zhu Qing, Wu Pinwen, Zhu Yi-Zhun, Mao Yicheng
Department of Pharmacology, the Key Laboratory of Smart Drug Delivery (Ministry of Education), School of Pharmacy, Minhang Hospital, Fudan University, Shanghai, China.
School of Pharmacy and Laboratory of Drug Discovery from Natural Resources and Industrializtion, Macau University of Science and Technology, Macau, China.
CNS Neurosci Ther. 2025 Feb;31(2):e70243. doi: 10.1111/cns.70243.
Ischemic stroke is well-known for its high mortality and morbidity, but its treatment remains to be explored due to the current limitations. For example, severe neuroinflammation occurs after ischemic stroke; however, effective neuroinflammatory inhibitors are still lacking. Thus, the development of new therapeutic targets of inhibiting neuroinflammation is urgent. CD24 is a small heavy glycosylated protein, which plays a critical role in neural development and acts as an inflammatory suppressor in tumors and autoimmune diseases. But the role of CD24 in ischemic stroke remains unknown.
The role of CD24 in ischemic stroke should be explored. Additionally, the potential relationship between the HS donor, S-propargyl-cysteine (SPRC) and CD24 in ischemic stroke should be revealed.
Mechanism studies have been performed both in vitro and in vivo to verify the CD24-mediated inflammation and migration. SPRC has been applied to treat ischemic stroke, and its potential association with CD24 has been studied.
The overexpression of CD24 can inhibit the nuclear factor kappa B (NF-κB) inflammatory signaling pathway and promote the migration ability of M2 microglia cells via Src/Fak/Pyk2 signaling pathway in an inflammatory model of BV2 cells. SPRC can upregulate the level of endogenous HS via cystathionase-β-synthase (CBS) and it indirectly plays a role in upregulating CD24.
CD24 could be a potential target of inhibiting neuroinflammation. SPRC reduces inflammation in ischemic stroke by regulating the CD24/Iκ-Bα/NF-κB inflammatory signaling pathway and improves the migration ability of M2 microglia via CD24/Src/Fak/Pyk2 signaling pathway, which further alleviates the inflammatory response at the lesion.
缺血性中风以其高死亡率和高发病率而闻名，但由于目前的局限性，其治疗方法仍有待探索。例如，缺血性中风后会发生严重的神经炎症；然而，仍然缺乏有效的神经炎症抑制剂。因此，开发抑制神经炎症的新治疗靶点迫在眉睫。CD24是一种小的重糖基化蛋白，在神经发育中起关键作用，在肿瘤和自身免疫性疾病中作为炎症抑制因子。但CD24在缺血性中风中的作用仍不清楚。
探索CD24在缺血性中风中的作用。此外，还应揭示硫化氢供体S-炔丙基半胱氨酸（SPRC）与缺血性中风中CD24之间的潜在关系。
在体外和体内进行机制研究，以验证CD24介导的炎症和迁移。应用SPRC治疗缺血性中风，并研究其与CD24的潜在关联。
在BV2细胞炎症模型中，CD24的过表达可抑制核因子κB（NF-κB）炎症信号通路，并通过Src/Fak/Pyk2信号通路促进M2小胶质细胞的迁移能力。SPRC可通过胱硫醚-β-合酶（CBS）上调内源性硫化氢水平，并间接上调CD24发挥作用。
CD24可能是抑制神经炎症的潜在靶点。SPRC通过调节CD24/Iκ-Bα/NF-κB炎症信号通路减轻缺血性中风中的炎症，并通过CD24/Src/Fak/Pyk2信号通路提高M2小胶质细胞的迁移能力，从而进一步减轻病变处的炎症反应。
