中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (7): 1043-1045.doi: 10.4103/1673-5374.187020

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

阿尔迪诺胶质细胞和RhoGTP酶活性调节是修复脊髓损伤的有效工具

  

  • 出版日期:2016-07-30 发布日期:2016-07-30

Aldynoglia cells and modulation of RhoGTPase activity as useful tools for spinal cord injury repair

Ernesto Doncel-Pérez1, *, Manuel Nieto-Sampedro2, *   

  1. 1 Grupo de Química Neuro-Regenerativa, Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla La Mancha (SESCAM), Toledo, Spain 2 Grupo de Plasticidad Neural, Instituto Cajal, CSIC, Madrid, Spain  
  • Online:2016-07-30 Published:2016-07-30
  • Contact: Ernesto Doncel-Pérez, Ph.D., ernestod@sescam.jccm.es or Manuel Nieto-Sampedro, Ph.D., mnietosampedro@gmail.com.

摘要:

中枢神经系统病变常常导致45岁以下人群丧失工作能力。虽然大脑或脊髓损伤的结果取决于受损面积和损伤程度,目前可用的治疗方法只能提供症状的缓解和康复。星形胶质细胞对中枢神经系统损伤的反应特征为产生硫酸软骨素蛋白多糖(CSPGs),这是对轴突再生来说是一道强有力的屏障。硫酸软骨素蛋白多糖的抑制作用已被归因于,该装饰蛋白质核带负电荷的葡萄糖胺聚糖链,充当差基板与静电排斥生长锥。蛋白酪氨酸磷酸酶西格马、白细胞共同抗原相关磷酸酶和Nogo受体已被确定为神经元受体在功能上相互作用并介导神经元生长的硫酸软骨素蛋白多糖依赖性抑制剂。软骨素酶ABC,即消化葡萄糖胺聚糖链的细菌酶,可以废除体外硫酸软骨素蛋白多糖依赖的轴突生长抑制剂并改善轴突生长和脊髓损伤后的功能恢复。因此,硫酸软骨素蛋白多糖受体的药物靶向是缓解CSPG依赖生长锥捕获的一种策略,并已经显示出一定的治疗潜力。虽然这些研究发现硫酸软骨素蛋白多糖受体是潜在的治疗靶标,今后的研究工作应重点开发小分子抑制剂,以实现伤后早期中枢神经系统更好的渗透和分布功能。我们考虑设计了糖苷酶抑制剂合成以实现星形胶质细胞的特异和时间抑制剂。反过来,这一方法将显著减少硫酸软骨素蛋白多糖的产生,进而促进轴突生长,神经元和胶质细胞的功能恢复。

orcid:0000-0002-2704-9782 (Ernesto Doncel-Pérez)

Abstract:

A combined approach in spinal cord injury (SCI) therapy is the modulation of the cellular and molecular processes involved in glial scarring. Aldaynoglial cells are neural cell precursors with a high capacity to differentiate into neurons, promote axonal growth, wrapping and myelination of resident neurons. These important characteristics of aldaynoglia can be combined with specific inhibition of the RhoGTPase activity in astroglia and microglia that cause reduction of glial proliferation, retraction of glial cell processes and myelin production by oligodendrocytes. Previously we used experimental central nervous system (CNS) injury models, like spinal cord contusion and striatal lacunar infarction and observed that administration of RhoGTPase glycolipid inhibitor or aldaynoglial cells, respectively, produced a significant gain of functional recovery in treated animals. The combined therapy with neuro-regenerative properties strategy is highly desirable to treat SCI for functional potentiation of neurons and oligodendrocytes, resulting in better locomotor recovery. Here we suggest that treatment of spinal lesions with aldaynoglia from neurospheres plus local administration of a RhoGTPase inhibitor could have an additive effect and promote recovery from SCI.

Key words: glial scar, astrocyte, microglia, neurospheres, aldaynoglia, axonal growth, myelination, glycoside inhibitor