Advanced Science丨TRIM56调节YBX1降解,改善脊髓损伤中ZBP1介导的神经元PANoptosis

主要观点总结

本文主要研究了在脊髓损伤（SCI）中，YBX1如何通过调节ZBP1介导的PANoptosis影响神经元的存活和功能恢复。同时，文章还探讨了E3泛素连接酶TRIM56作为YBX1的内源性抑制剂，如何通过泛素化促进YBX1的降解。实验结果揭示了YBX1、ZBP1和TRIM56之间的相互作用及其在小鼠脊髓损伤后的功能作用。

关键观点总结

关键观点1: YBX1在脊髓损伤后的神经元中表达增加，并通过稳定Zbp1 mRNA促进ZBP1的表达，从而加剧ZBP1介导的PANoptosis。

研究发现，YBX1的表达在受伤神经元中高度增加，并通过稳定Zbp1 mRNA来促进ZBP1的蛋白表达。YBX1的敲除有利于脊髓损伤后的功能恢复。

关键观点2: TRIM56被鉴定为YBX1的内源性抑制剂，通过与YBX1结合促进其泛素化，从而加速YBX1的降解。

研究结果表明，TRIM56与YBX1之间存在直接相互作用，TRIM56通过泛素化促进YBX1的降解。TRIM56的过度表达或敲除会影响YBX1的表达和稳定性。

关键观点3: TRIM56通过调节YBX1的表达影响神经元PANoptosis和脊髓损伤后的功能恢复。

实验结果显示，敲除TRIM56会通过促进YBX1的表达，加剧神经元的PANoptosis并限制脊髓损伤后的功能恢复。这为脊髓损伤的治疗提供了新的见解。

文章预览

Chestnut Studying       摘要  Spinal cord injury (SCI) is a severe injury to the central nervous system, and its treatment is always a major medical challenge. Proinflammatory cell death is considered an important factor affecting neuroinflammation and the prognosis after injury. PANoptosis, a newly discovered type of proinflammatory cell death, regulates the activation of executioner molecules of apoptosis, pyroptosis and necroptosis through the PANoptosome, providing a new target for therapeutic intervention after SCI. However, its role and regulatory mechanism in SCI are not yet elucidated. Here, based on proteomic data, YBX1 expression is significantly increased in neurons after SCI. Guided by RIP-seq, subsequent experiments reveal that YBX1 promotes ZBP1 expression by stabilizing the Zbp1 mRNA, thereby aggravating ZBP1-mediated PANoptosis. Furthermore, the E3 ubiquitin ligase TRIM56 is identified as an endogenous inhibitor of YBX1 via molecular docking and IP/MS analysis. M ………………………………