Rho Signaling Pathway Targeted to Promote Spinal Cord Repair
Rho Signaling Pathway Targeted to Promote Spinal Cord Repair
复制标题
DOI：
10.1523/jneurosci.22-15-06570.2002
复制
发表时间：
2002-08
期刊：
影响因子：
--
通讯作者：
P. Dergham;B. Ellezam;C. Essagian;H. Avedissian;W. Lubell;L. Mckerracher
中科院分区：
文献类型：
--
作者：
P. Dergham;B. Ellezam;C. Essagian;H. Avedissian;W. Lubell;L. Mckerracher
The Rho signaling pathway regulates the cytoskeleton and motility and plays an important role in neuronal growth inhibition. Here we demonstrate that inactivation of Rho or its downstream target Rho-associated kinase (ROK) stimulated neurite growth in primary cells of cortical neurons plated on myelin or chondroitin sulfate proteoglycan substrates. Furthermore, treatment either with C3 transferase (C3) to inactivate Rho or with Y27632 to inhibit ROK was sufficient to stimulate axon regeneration and recovery of hindlimb function after spinal cord injury (SCI) in adult mice. Injured mice were treated with a single injection of Rho or Rho-associated kinase inhibitors delivered in a protein adhesive at the lesion site. Treated animals showed long-distance regeneration of anterogradely labeled corticospinal axons and increased levels of GAP-43 mRNA in the motor cortex. Behaviorally, inactivation of Rho pathway induced rapid recovery of locomotion and progressive recuperation of forelimb–hindlimb coordination. These findings provide evidence that the Rho signaling pathway is a potential target for therapeutic interventions after spinal cord injury.
