A New Role for RPTPσ in Spinal Cord Injury: Signaling Chondroitin Sulfate Proteoglycan Inhibition
A New Role for RPTPσ in Spinal Cord Injury: Signaling Chondroitin Sulfate Proteoglycan Inhibition
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DOI：
10.1126/scisignal.3110pe6
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发表时间：
2010-02-23
影响因子：
7.3
通讯作者：
Giger, Roman J.
中科院分区：
文献类型：
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作者：
Duan, Yuntao;Giger, Roman J.
二十多年来，人们已经知道硫酸软骨素蛋白多糖(CSPGs)可以抑制轴突的生长和再生。在成人神经系统中，CSPG在神经周网络中丰富，在脑或脊髓损伤后，其在反应性星形胶质细胞中的丰度增加。通过局部注射细菌酶软骨素酶ABC(ChaseABC)降解硫酸软骨素(CS)糖部分可增强成年视皮层中经验依赖性神经元的可塑性，并显著改善脊髓损伤(SCI)后的行为结果。虽然ChaseABC治疗对神经元可塑性的积极影响已经被知道了一段时间，但其潜在的机制仍然是个谜。受体蛋白酪氨酸磷酸酶Sigma(RPTP Sigma)现已被确定为抑制性CSPGs的受体。与ChaseABC治疗相似，功能性消融编码RPTP sigma的基因Ptprs在体外促进CSPG存在下的轴突生长，并促进轴突生长到体内SCI后富含CSPG的瘢痕组织。神经元RPTP sigma作为抑制性CSPG受体的发现，不仅为研究CSPG的功能提供了重要的机制线索，而且为促进神经系统损伤后轴突的生长和可塑性提供了一个潜在的新靶点。
It has been known for more than two decades that chondroitin sulfate proteoglycans (CSPGs) inhibit axonal growth and regeneration. In the adult nervous system, CSPGs are enriched in perineuronal nets, and their abundance is increased in reactive astrocytes following injury to brain or spinal cord. Degradation of chondroitin sulfate (CS) sugar moieties by the local infusion of the bacterial enzyme chondroitinase ABC (ChaseABC) enhances experience-dependent neuronal plasticity in the adult visual cortex and results in substantially improved behavioral outcomes after spinal cord injury (SCI). Although the positive effects of ChaseABC treatment on neuronal plasticity have been known for some time, the underlying mechanisms remained enigmatic. The receptor protein tyrosine phosphatase sigma (RPTP sigma) has now been identified as a receptor for inhibitory CSPGs. Similarly to ChaseABC treatment, functional ablation of Ptprs, the gene encoding RPTP sigma, promotes neurite outgrowth in the presence of CSPGs in vitro and enhances axonal growth into CSPG-rich scar tissue following SCI in vivo. The discovery of neuronal RPTP sigma as a receptor for inhibitory CSPGs not only provides important mechanistic clues about CSPG function, but also identifies a potential new target for enhancing axonal growth and plasticity after nervous system injury.