Department of Cell and Developmental Biology and Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Sci Signal. 2010 Feb 23;3(110):pe6. doi: 10.1126/scisignal.3110pe6.
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 (RPTPsigma) has now been identified as a receptor for inhibitory CSPGs. Similarly to ChaseABC treatment, functional ablation of Ptprs, the gene encoding RPTPsigma, 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 RPTPsigma 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.
二十多年来，人们已经知道软骨素硫酸盐蛋白聚糖（CSPGs）会抑制轴突的生长和再生。在成人的神经系统中，CSPGs 富含于神经元周围的网络中，并且在大脑或脊髓受伤后，反应性星形胶质细胞中的 CSPGs 含量会增加。局部输注细菌酶软骨素酶 ABC（ChaseABC）可降解软骨素硫酸盐（CS）的糖基部分，从而增强成年视觉皮层中经验依赖性的神经元可塑性，并在脊髓损伤（SCI）后显著改善行为结果。尽管 ChaseABC 治疗对神经元可塑性的积极影响已经为人所知一段时间了，但潜在的机制仍然是个谜。受体蛋白酪氨酸磷酸酶 sigma（RPTPsigma）现已被确定为抑制性 CSPGs 的受体。与 ChaseABC 治疗类似，基因 Ptprs（编码 RPTPsigma）的功能性缺失促进了体外 CSPGs 存在时的神经突生长，并增强了体内 SCI 后 CSPG 丰富的瘢痕组织中的轴突生长。神经元 RPTPsigma 作为抑制性 CSPGs 的受体的发现不仅为 CSPG 功能提供了重要的机制线索，而且还确定了一个增强神经系统损伤后轴突生长和可塑性的潜在新靶点。
