Translational Studied of Chondroitin Sulfate Proteoglycans

该项目的目的是开发治疗脑和脊髓损伤的潜在方法。一种方法是限制硫酸软骨素蛋白多糖(CSPGs)的生产或增加其降解率。 我们已经证明，仅在非还原端将4-硫酸酯基团从硫酸软骨素中分离出来的芳基硫酸酯酶B(ARSB)，可以显著促进硫酸软骨素底物上神经元的生长。我们研究了CSPGS在视神经挤压后视神经损伤中的作用。我们已经证明了CSPG在小鼠视神经中的显著上调。我们还表明，ARSB可以显著促进视神经挤压后小鼠视神经轴突的再生。描述这些结果的手稿已经出版。一份后续的手稿正在审查中，该手稿确定了视神经挤压后蛋白多糖组成的变化。 我们现在正在研究在视神经挤压模型中通过改变神经元细胞内信号通路来促进轴突生长的药物的使用。初步数据是正面的。

The objective of this project is to develop potential approaches to the therapy of brain and spinal cord injury. One approach is to limit the production or increase the degradation of chondroitin sulfate proteoglycans (CSPGs). We have demonstrated that the enzyme arylsulfatase B (ARSB), which cleaves the 4-sulfate group from chondroitin sulfate only at the non-reducing end, can dramatically increase neuronal growth on substrates of chondroitin sulfate. We have investigated the role of CSPGS in the injured optic nerve following optic nerve crush. We have demonstrated a significant upregulation of CSPGs in the moue optic nerve. We have also shown that ARSB can significantly improve the regeneration of axons in the mouse optic nerve following optic nerve crush. A manuscript describing these results has been published. A follow-up manuscript is under review which identifies the changes in proteoglycan composition following optic nerve crush. We are now investigating the use of agents which promote axonal growth by altering neuronal intracellular signaling pathways in the optic nerve crush model. Preliminary data are positive.