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Roles of CSGalNAcT1, a key enzyme in regulation of CS synthesis, in neuronal regeneration and plasticity
Neurochemistry international ( IF 4.2 ) Pub Date : 2017-10-05 , DOI: 10.1016/j.neuint.2017.10.001
Michihiro Igarashi , Kosei Takeuchi , Sayaka Sugiyama

Chondroitin sulfate (CS) is a sulfated glycosaminoglycan composed of a long chain of repeating disaccharide units that are attached to core proteins, resulting in CS proteoglycans (CSPGs). In the mature brain, CS is concentrated in perineuronal nets (PNNs), which are extracellular structures that surround synapses and regulate synaptic plasticity. In addition, CS is rapidly synthesized after CNS injury to create a physical and chemical barrier that inhibits axon growth. Most previous studies used a bacterial CS-degrading enzyme to investigate the physiological roles of CS. Recent studies have shown that CS is synthesized by more than 15 enzymes, all of which have been characterized in vitro. Here we focus on one of those enzymes, CSGalNAcT1 (T1). We produced T1 knockout mice (KO), which show extensive axon regeneration following spinal cord injury, as well as the loss of onset of ocular dominance plasticity. These results from T1KO mice suggest important roles for extracellular CS in the brain regarding neuronal plasticity and axon regeneration.



中文翻译:

调节CS合成的关键酶CSGalNAcT1在神经元再生和可塑性中的作用

硫酸软骨素(CS)是一种硫酸化的糖胺聚糖,由连接至核心蛋白的长链重复双糖单元组成,从而产生CS蛋白聚糖(CSPG)。在成熟的大脑中,CS集中在神经周围神经网络(PNN)中,神经网络是围绕突触并调节突触可塑性的细胞外结构。另外,CS在CNS损伤后迅速合成以产生抑制轴突生长的物理和化学屏障。以前的大多数研究都使用细菌CS降解酶来研究CS的生理作用。最近的研究表明CS是由15种以上的酶合成的,所有这些酶均已在体外进行了表征。在这里,我们集中于这些酶之一,CSGalNAcT1(T1)。我们生产了T1基因敲除小鼠(KO),其在脊髓损伤后显示出广泛的轴突再生,以及丧失了眼部优势可塑性的发作。T1KO小鼠的这些结果表明,在神经元可塑性和轴突再生方面,细胞外CS在大脑中起着重要作用。

更新日期:2017-10-05
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