Proteoglycan Sulphation in the Function of the Mature Central Nervous System.
Proteoglycan Sulphation in the Function of the Mature Central Nervous System.
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DOI：
10.3389/fnint.2022.895493
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发表时间：
2022
影响因子：
3.5
通讯作者：
Kwok, Jessica C. F.
中科院分区：
文献类型：
--
作者：
Fawcett, James W.;Kwok, Jessica C. F.
关键词：
硫酸软骨素和硫酸乙酰肝素蛋白聚糖（CSPGS和HSPG）在整个中枢神经系统（CNS）中发现。CSPG普遍存在于细胞之间的弥散性细胞外基质（ECM）中，并且是神经元周网（PNN）的主要组分，所述神经元周网是存在于一些神经元周围的浓缩ECM。HSPGs更多地与神经元和胶质细胞的表面、突触和PNN相关。CSPG和HSPG均由蛋白质核心组成，在该蛋白质核心上连接有通过在不同位置处硫酸化修饰的重复二糖链。硫酸化的顺序使链具有独特的结构和局部电荷密度。这些硫酸化密码控制蛋白聚糖的结合特性和生物学效应。CSPG沿其长度沿着被硫酸化，主要形式为6-和4-硫酸化。通常，软骨素4-硫酸盐抑制细胞附着和迁移，而软骨素6-硫酸盐更允许。HSPG倾向于在孤立的基序中被硫酸化，其间具有未硫酸化的区域。HS基序和CS聚糖链的硫酸化模式控制它们与PTPsigma受体的结合以及许多效应分子与蛋白聚糖的结合，例如生长因子、形态发生素和参与神经退行性疾病的分子。硫酸化模式会因损伤、炎症和老化而改变。对于CSPGs，注意力集中在PNN及其在可塑性和记忆控制中的作用，以及在胶质瘢痕组织中上调的可溶性CSPGs，其可以抑制轴突再生。HSPG在发育、调节细胞迁移和轴突生长中具有关键作用。在成年CNS中，它们与tau聚集和淀粉样蛋白-β加工、突触发生、生长因子信号传导相关，并作为干细胞生态位的组成部分。CSPG和HSPG的这些功能受到聚糖链硫酸化模式（硫酸化密码）的强烈影响。本文综述了这些硫酸化模式及其对成熟中枢神经系统功能的影响。
Chondroitin sulphate and heparan sulphate proteoglycans (CSPGS and HSPGs) are found throughout the central nervous system (CNS). CSPGs are ubiquitous in the diffuse extracellular matrix (ECM) between cells and are a major component of perineuronal nets (PNNs), the condensed ECM present around some neurons. HSPGs are more associated with the surface of neurons and glia, with synapses and in the PNNs. Both CSPGs and HSPGs consist of a protein core to which are attached repeating disaccharide chains modified by sulphation at various positions. The sequence of sulphation gives the chains a unique structure and local charge density. These sulphation codes govern the binding properties and biological effects of the proteoglycans. CSPGs are sulphated along their length, the main forms being 6- and 4-sulphated. In general, the chondroitin 4-sulphates are inhibitory to cell attachment and migration, while chondroitin 6-sulphates are more permissive. HSPGs tend to be sulphated in isolated motifs with un-sulphated regions in between. The sulphation patterns of HS motifs and of CS glycan chains govern their binding to the PTPsigma receptor and binding of many effector molecules to the proteoglycans, such as growth factors, morphogens, and molecules involved in neurodegenerative disease. Sulphation patterns change as a result of injury, inflammation and ageing. For CSPGs, attention has focussed on PNNs and their role in the control of plasticity and memory, and on the soluble CSPGs upregulated in glial scar tissue that can inhibit axon regeneration. HSPGs have key roles in development, regulating cell migration and axon growth. In the adult CNS, they have been associated with tau aggregation and amyloid-beta processing, synaptogenesis, growth factor signalling and as a component of the stem cell niche. These functions of CSPGs and HSPGs are strongly influenced by the pattern of sulphation of the glycan chains, the sulphation code. This review focuses on these sulphation patterns and their effects on the function of the mature CNS.
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DOI：
10.1093/brain/awy158
发表时间：
2018-08-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Burnside ER;De Winter F;Didangelos A;James ND;Andreica EC;Layard-Horsfall H;Muir EM;Verhaagen J;Bradbury EJ
通讯作者：
Bradbury EJ
影响因子：
4.8
作者：
Dick, Gunnar;Tan, Chin Lik;Kwok, Jessica C. F.
通讯作者：
Kwok, Jessica C. F.
影响因子：
5.2
作者：
Akita, Kaoru;von Holst, Alexander;Faissner, Andreas
通讯作者：
Faissner, Andreas
影响因子：
15.9
作者：
Esko, JD;Lindahl, U
通讯作者：
Lindahl, U
影响因子：
3.3
作者：
Lazaro-Pena, Maria I.;Diaz-Balzac, Carlos A.;Emmons, Scott W.
通讯作者：
Emmons, Scott W.