Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta Canada.
Autoimmun Rev. 2011 Oct;10(12):766-72. doi: 10.1016/j.autrev.2011.05.019. Epub 2011 Jun 2.
The extracellular matrix (ECM) is a complex network of scaffolding molecules that also plays an important role in cell signalling, migration and tissue structure. In the central nervous system (CNS), the ECM is integral to the efficient development/guidance and survival of neurons and axons. However, changes in distribution of the ECM in the CNS may significantly enhance pathology in CNS disease or following injury. One group of ECM proteins that is important for CNS homeostasis is the chondroitin sulphate proteoglycans (CSPGs). Up-regulation of these molecules has been demonstrated to be both desirable and detrimental following CNS injury. Taking cues from arthritis, where there is a strong anti-CSPG immune response, there is evidence that suggests that CSPGs may influence immunity during CNS pathological conditions. This review focuses on the role of CSPGs in CNS pathologies as well as in immunity, both from a viewpoint of how they may inhibit repair and exacerbate damage in the CNS, and how they are involved in activation and function of peripheral immune cells, particularly in multiple sclerosis. Lastly, we address how CSPGs may be manipulated to improve disease outcomes.
细胞外基质 (ECM) 是一种复杂的支架分子网络，在细胞信号转导、迁移和组织结构中也起着重要作用。在中枢神经系统 (CNS) 中，ECM 对于神经元和轴突的有效发育/导向和存活至关重要。然而，CNS 中 ECM 的分布变化可能会显著增强 CNS 疾病或损伤后的病理学。一组对 CNS 稳态很重要的 ECM 蛋白是软骨素硫酸盐蛋白聚糖 (CSPGs)。已经证明，这些分子的上调在 CNS 损伤后既有可取之处，也有不利之处。从关节炎中得到提示，关节炎中有强烈的抗 CSPG 免疫反应，有证据表明 CSPGs 可能会影响 CNS 病理条件下的免疫。本综述重点讨论了 CSPGs 在 CNS 病理中的作用以及在免疫中的作用，既包括它们如何抑制 CNS 中的修复并加剧损伤，又包括它们如何参与外周免疫细胞的激活和功能，特别是在多发性硬化症中。最后，我们探讨了如何操纵 CSPGs 以改善疾病结局。
