Avram Speranta, Shaposhnikov Sergey, Buiu Catalin, Mernea Maria
Anatomy, Animal Physiology and Biophysics Department, Faculty of Biology, University of Bucharest, 91-95th Independentei Street, 050095 Bucharest, Romania.
Norgenotech AS, Totenvegen 2049, 2848 Skreia, Norway.
Biomed Res Int. 2014;2014:642798. doi: 10.1155/2014/642798. Epub 2014 May 14.
Chondroitin sulfate proteoglycans (CSPGS) are extracellular matrix components that contain two structural parts with distinct functions: a protein core and glycosaminoglycan (GAG) side chains. CSPGs are known to be involved in important cell processes like cell adhesion and growth, receptor binding, or cell migration. It is recognized that the presence of CSPGs is critical in neuronal growth mechanisms including axon guidance following injury of nervous system components such as spinal cord and brain. CSPGs are upregulated in the central nervous system after injury and participate in the inhibition of axon regeneration mainly through their GAG side chains. Recently, it was shown that some CSPGs members like aggrecan, versican, and neurocan were strongly involved in brain disorders like bipolar disorder (BD), schizophrenia, and ADHD. In this paper, we present the chemical structure-biological functions relationship of CSPGs, both in health state and in genetic disorders, addressing methods represented by genome-wide and crystallographic data as well as molecular modeling and quantitative structure-activity relationship.
硫酸软骨素蛋白聚糖(CSPGs)是细胞外基质成分,包含两个具有不同功能的结构部分:一个蛋白核心和糖胺聚糖(GAG)侧链。已知CSPGs参与重要的细胞过程,如细胞黏附与生长、受体结合或细胞迁移。人们认识到,CSPGs的存在在神经元生长机制中至关重要,包括在脊髓和脑等神经系统成分损伤后的轴突导向。损伤后,CSPGs在中枢神经系统中上调,并主要通过其GAG侧链参与轴突再生的抑制。最近,研究表明一些CSPGs成员,如聚集蛋白聚糖、多功能蛋白聚糖和神经蛋白聚糖,与双相情感障碍(BD)、精神分裂症和注意力缺陷多动障碍等脑部疾病密切相关。在本文中,我们阐述了CSPGs在健康状态和遗传疾病中的化学结构-生物学功能关系,探讨了以全基因组和晶体学数据以及分子建模和定量构效关系为代表的方法。