化疗引起的认知障碍（CICI）是神经科学和肿瘤学中需要关键解决方案的课题。然而，其潜在的作用机制仍然不明确。本研究的目的是探讨 HuR 在甲氨蝶呤 (MTX) 诱导的认知障碍期间环孢素 A (CsA) 的神经保护中的重要作用。一系列 Hu 抗原 R (HuR) 获得和丢失实验用于检测环孢菌素 A (CsA) 介导的 HuR 易位通过 NCOA4 介导的铁蛋白自噬改善 MTX 诱导的认知障碍的能力。获得的结果表明，给予 CsA 可以减轻 MTX 诱导的小鼠认知障碍。 MTX 的存在促进了 HuR 从细胞质到细胞核的穿梭，而与 MTX 组相比，CsA 处理增加了细胞质 HuR 表达水平和铁蛋白自噬相关蛋白（如 NCOA4 和 LC3II）的水平。然而，应用 HuR 抑制剂 KH-3 逆转了 CsA 对海马和体外铁蛋白自噬相关蛋白表达的影响。此外，CsA 治疗可通过改变 Iba-1 表达来减弱小胶质细胞的活化，并降低小鼠海马中 TNF-α 和 IL-1β 的水平。此外，KH-3 中和了 CsA 对体内和体外 Iba-1 和 HuR 表达的影响。综上所述，CsA被证实在CICI中具有神经保护作用。其可能的潜在机制可能涉及HuR的易位。在 CICI 期间介导 HuR 的易位可以通过 NCOA4 介导的铁蛋白自噬减轻神经炎症和神经元凋亡，从而减轻 CICI 小鼠的认知障碍。

Chemotherapy-induced cognitive impairment (CICI) is a subject that requires critical solutions in neuroscience and oncology. However, its potential mechanism of action remains ambiguous. The aim of this study was to investigate the vital role of HuR in the neuroprotection of cyclosporin A (CsA) during methotrexate (MTX)-induced cognitive impairment. A series of Hu-antigen R (HuR) gain and loss experiments were used to examine cyclosporin A (CsA)-mediated translocation of HuR's ability to improve MTX-induced cognitive impairment through NCOA4-mediated ferritinophagy in vitro and in vivo. Obtained results show that the administration of CsA alleviated MTX-induced cognitive impairment in mice. The presence of MTX promoted the shuttling of HuR from the cytoplasm to the nucleus, whereas treatment with CsA increased cytoplasmic HuR expression levels and the levels of ferritinophagy-related proteins, such as NCOA4 and LC3II, compared to the MTX group. However, applying KH-3, an inhibitor of HuR, reversed CsA's impact on the expression of ferritinophagy-related proteins in the hippocampus and in vitro. Also, treatment with CsA attenuated microglial activation by altering Iba-1 expression and decreased TNF-α and IL-1β levels in mice hippocampi. Moreover, KH-3 neutralized CsA's effects on the expression of both Iba-1 and HuR in vivo and in vitro. In summary, CsA was confirmed to have a neuroprotective role in CICI. Its possible underlying mechanisms may be involved in the translocation of HuR. Mediating the translocation of HuR during CICI could mitigate neruoinflammation and neuronal apoptosis via NCOA4-mediated ferritinophagy and, thus, alleviate cognitive impairment in mice with CICI.