RhoA as a target to promote neuronal survival and axon regeneration  

作　　者：Jianli Hu Michael E. Seizer 

机构地区：[1]Shriners Hospitals for Children, Pediatric Research Center (Center for Neural Repair and Rehabilitation), Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA [2]Department of Neurology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

出　　处：《Neural Regeneration Research》2017年第4期525-528,共4页中国神经再生研究（英文版）

基　　金：supported by R01-NS092876(NIH,MES,PI);SHC-85400(Shriners Research Foundation,MES,PI);SHC-85220(Shriners Research Foundation,MES,PI);SHC-84293(Shriners Research Foundation,JH,PI)

摘　　要：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.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.

关 键 词：RHOA spinal cord injury neuronal survival apoptosis axon regeneration MORPHOLINO C3 transferase 

分 类 号：R744[医药卫生—神经病学与精神病学]