RhoA as a target to promote neuronal survival and axon regeneration.
RhoA as a target to promote neuronal survival and axon regeneration.
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DOI：
10.4103/1673-5374.205080
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发表时间：
2017-04
影响因子：
6.1
通讯作者：
Selzer ME
中科院分区：
文献类型：
--
作者：
Hu J;Selzer ME
脊髓损伤（SCI）后的瘫痪是由于轴突再生失败造成的。据信，神经元再生其轴突的能力部分是由于其内在特性，这反过来又受到存在的几种类型的抑制分子的极大影响，甚至在受损脊髓的细胞外环境中增加。近年来，这些抑制性分子中的许多已被广泛研究。已经提出小GTdR RhoA是这些细胞外抑制分子信号传导的细胞内会聚点，但由于哺乳动物中枢神经系统（CNS）的复杂性和药理学工具的限制，RhoA的具体作用尚不清楚。通过利用七鳃鳗中枢神经系统的解剖学和技术优势，我们最近证明了RhoA敲低促进SCI后损伤部位的真正轴突再生。此外，我们发现RhoA基因敲低可保护大的、已鉴定的网状脊髓神经元在其轴突在脊髓中被切断后免于凋亡。因此，操纵RhoA信号通路可能是开发神经保护和轴突再生促进治疗的重要方法，以增强SCI后的功能恢复。
Paralysis following spinal cord injury (SCI) is due to failure of axonal regeneration. It is believed that the capacities of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase RhoA is an intracellular convergence point for signaling by these extracellular inhibitory molecules, but due to the complexity of the central nervous system (CNS) in mammals, and the limitation of pharmacological tools, the specific roles of RhoA are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently demonstrated that RhoA knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that RhoA knockdown protects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the RhoA signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI.