Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
Departamento de Biología Funcional, Área de Fisiología, Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
Biomolecules. 2020 Mar 5;10(3):403. doi: 10.3390/biom10030403.
Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, proliferation, and migration, as well as to support for various signaling pathways. In the central nervous system (CNS), proteoglycans of the lectican family, such as versican, aggrecan, brevican, and neurocan, are important constituents of the ECM. In recent years, members of this family have been found to be involved in the maintenance of CNS homeostasis and to participate directly in processes such as the organization of perineural nets, the regulation of brain plasticity, CNS development, brain injury repair, axonal guidance, and even the altering of synaptic responses. ADAMTSs are a family of "A disintegrin and metalloproteinase with thrombospondin motifs" proteins that have been found to be involved in a multitude of processes through the degradation of lecticans and other proteoglycans. Recently, alterations in ADAMTS expression and activity have been found to be involved in neuronal disorders such as stroke, neurodegeneration, schizophrenia, and even Alzheimer's disease, which in turn may suggest their potential use as therapeutic targets. Herein, we summarize the different roles of ADAMTSs in regulating CNS events through interactions and the degradation of ECM components (more specifically, the lectican family of proteoglycans).
细胞外基质(ECM)的成分是调节整个生物体细胞功能的关键因素。事实上,ECM 成分不仅参与组织的构成,而且有助于细胞的维持、增殖和迁移等过程,以及支持各种信号通路。在中枢神经系统(CNS)中,聚集蛋白聚糖家族的蛋白聚糖,如 versican、aggrecan、brevican 和 neurocan,是 ECM 的重要组成部分。近年来,该家族的成员被发现参与中枢神经系统的内稳态维持,并直接参与神经网的组织、脑可塑性的调节、中枢神经系统的发育、脑损伤修复、轴突导向,甚至改变突触反应等过程。ADAMTSs 是一类“含有解整合素和金属蛋白酶基序的 A 型血小板反应蛋白”蛋白,它们通过降解聚集蛋白聚糖和其他蛋白聚糖,参与了多种过程。最近,ADAMTSs 的表达和活性的改变被发现与神经元疾病有关,如中风、神经退行性变、精神分裂症,甚至阿尔茨海默病,这反过来可能表明它们有作为治疗靶点的潜力。在此,我们总结了 ADAMTSs 通过与 ECM 成分(更具体地说,是聚集蛋白聚糖家族的蛋白聚糖)的相互作用和降解,在调节中枢神经系统事件中的不同作用。