运动神经源性蛋白Agrin在神经瘢痕抑制中对神经再生选择性的影响及作用机制

Peripheral nerve regeneration has been extensively studied in the field of physical rehabilitation. However, existing studies mainly focus on quantity rather than quality of regenerated nerves. The motor-neuron-derived protein agrin, a pathway-specific protein, is closely related to the regeneration of motor nerves. We have proved in previous researches that nano-ethosomes carrying 5-fluorouracil can inhibit the proliferation of peripheral nerve scar tissue and raise the expression levels of agrin. The aim of this study is to further explore how 5-fluorouracil interacts with signaling molecules including agrin and the effects of those interactions on how the GTPases Rho family manages preferential nerve regeneration. In this study, we used fluorescencenear-infrared probes for in vivo imaging and were able to achieve real-time quantitative tracing. According to our findings, the nano-ethosomal encapsulated with 5-fluorouracil expand extracellular space to facilitate the advancement of nerve sprouts and is also involved in the signaling pathway Agrin-NCAM-Pak1-GTPases Rho for preferential peripheral nerve regeneration. Furthermore, this study elucidates the molecular mechanisms of signaling pathways that regulate target-selective peripheral nerve regeneration. Our work provides a new perspective and effective methods to promote target-selective reinnervation, thus shifting the focus from quantity to quality in peripheral nerve regeneration.

周围神经再生修复一直是运动康复领域研究重点，目前研究策略多集中于促进神经再生“数量”，但对于如何提高再生神经的“质量”的研究并不多。运动神经源性蛋白Agrin作为特异性路径蛋白，与运动神经的再生关系密切。本项目前期研究发现纳米级5-FU醇脂体抑制周围神经瘢痕增生过程中，还可促进Agrin表达升高。为深入研究其与Agrin等信号分子相互作用及对GTPases Rho家族调节神经再生选择性的影响，本项目结合前期活体成像的近红外荧光探针技术，实现体内实时定量化示踪，揭示纳米级5-FU醇脂体在为再生新芽创造行进空间同时，对周围神经再生选择性的路径信号通路Agrin-NCAM-Pak1-GTPases Rho的影响，阐明周围神经再生过程中调控再生神经靶标投射选择性的相关路径信号通路分子机制，为实现周围神经修复量变到质变，促进再生神经纤维精准靶向投射的有质量的支配功能，提供科学有效的新方法和思路。

周围神经再生修复是运动康复领域研究重点，目前研究策略多集中于促进神经再生“数量”，但对于如何提高再生神经的“质量”的研究并不多。运动神经源性蛋白Agrin作为特异性路径蛋白，与运动神经的再生关系密切。本项目前期研究发现纳米级5-FU醇脂体抑制周围神经瘢痕增生过程中，促进Agrin表达升高。为深入研究其与Agrin等信号分子相互作用及对GTPases Rho家族调节神经再生选择性的影响，本项目结合前期活体成像的近红外荧光探针技术，实现体内实时定量化示踪，揭示纳米级5-FU醇脂体在为再生新芽创造行进空间同时，对周围神经再生选择性的路径信号通路Agrin-NCAM-Pak1-GTPases Rho的影响，阐明周围神经再生过程中调控再生神经靶标投射选择性的相关路径信号通路分子机制，为实现周围神经修复量变到质变，促进再生神经纤维精准靶向投射的有质量的支配功能，提供科学有效的新方法和思路。