Department for Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany.
Mol Neurobiol. 2016 Jan;53(1):73-82. doi: 10.1007/s12035-014-8990-4. Epub 2014 Nov 18.
The extracellular matrix (ECM) of the central nervous system (CNS) occupies a large part of the neural tissue. It serves a variety of functions ranging from support of cell migration and regulating synaptic transmission and plasticity to the active modulation of the neural tissue after injury. In addition, evidence for neuroprotective properties of ECM components has accumulated more recently. In contrast to other connective tissues, the central nervous ECM is mainly composed of glycosaminoglycans, which can be present unbound in the form of hyaluronan or bound to proteins, thus forming proteoglycans. A subtype of this molecular family are the chondroitin sulphate proteoglycans (CSPGs), which are composed of a core protein that carries at least one covalently bound glycosaminoglycan side chain with a certain degree of sulphation. Several studies could show neuroprotective features of CSPGs against excitotoxicity, amyloid-ß toxicity, or oxidative stress. Recently, we could provide evidence for a neuroprotective function of a specialized form of ECM, the so-called perineuronal net ensheathing a subtype of neurons. Here, we will give an overview on recently emerging aspects of neuroprotective properties of CSPGs and perineuronal nets that might be relevant for our understanding on the distribution and progression of brain pathology and future perspectives toward modifying neurodegenerative diseases.
中枢神经系统(CNS)的细胞外基质(ECM)占据了神经组织的很大一部分。它具有多种功能,从支持细胞迁移和调节突触传递和可塑性,到损伤后对神经组织的主动调节。此外,最近积累了 ECM 成分具有神经保护特性的证据。与其他结缔组织不同,中枢神经系统 ECM 主要由糖胺聚糖组成,它们可以以透明质酸的未结合形式存在,也可以与蛋白质结合形成蛋白聚糖。该分子家族的一个亚型是软骨素硫酸盐蛋白聚糖(CSPGs),由至少一个共价结合的糖胺聚糖侧链组成,其具有一定程度的硫酸化。有几项研究表明 CSPGs 具有对抗兴奋毒性、淀粉样蛋白-β毒性或氧化应激的神经保护作用。最近,我们提供了证据表明,一种特殊形式的 ECM,即所谓的围绕神经元的神经周细胞网络,具有神经保护功能。在这里,我们将概述 CSPGs 和神经周细胞网络的神经保护特性的最新研究进展,这些进展可能与我们对脑病理学分布和进展的理解以及未来针对神经退行性疾病的治疗方法有关。