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化学酶法合成的GM3类似物作为潜在治疗剂,通过诱导神经突生长来恢复损伤后的神经功能。

Chemoenzymatically synthesized GM3 analogues as potential therapeutic agents to recover nervous functionality after injury by inducing neurite outgrowth.

作者信息

Zheng Changping, Qu Huanhuan, Liao Wenfeng, Bavaro Teodora, Terreni Marco, Sollogoub Matthieu, Ding Kan, Zhang Yongmin

机构信息

Sorbonne Université, CNRS, UMR 8232, IPCM, 4 Place Jussieu, 75005 Paris, France.

Glycochemistry & Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Pudong, Shanghai 201203, China.

出版信息

Eur J Med Chem. 2018 Feb 25;146:613-620. doi: 10.1016/j.ejmech.2018.01.079. Epub 2018 Jan 31.

DOI:10.1016/j.ejmech.2018.01.079
PMID:29407985
Abstract

Ganglioside GM3 is implicated in a variety of physiological and pathological processes. Due to GM3 exposes on the outer surface of cell membranes, it is strongly associated with cell adhesion, motility and differentiation. Neurite outgrowth is a key process in the development of functional neuronal circuits and regeneration of the nervous system after injury. In the present study, we used enzymatic hydrolysis and chemical synthesis to obtain novel galactose containing GM3 analogues. By enzymatic hydrolysis to prepare GM3 building block, we can avoid multiple chemical procedures. Next, we employed the PC12 cells as a model to evaluate the effects of GM3 analogues on neurite outgrowth with or without NGF induction. The biological tests showed that GM3 analogues could induce neurite outgrowth, which provides the valuable sights for potential nervous system treatment after injury.

摘要

神经节苷脂GM3与多种生理和病理过程有关。由于GM3暴露于细胞膜外表面,它与细胞黏附、运动和分化密切相关。神经突生长是功能性神经回路发育和损伤后神经系统再生的关键过程。在本研究中,我们使用酶水解和化学合成方法获得了含半乳糖的新型GM3类似物。通过酶水解制备GM3构建块,我们可以避免多个化学步骤。接下来,我们以PC12细胞为模型,评估GM3类似物在有无NGF诱导情况下对神经突生长的影响。生物学测试表明,GM3类似物可诱导神经突生长,这为损伤后潜在的神经系统治疗提供了有价值的见解。

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引用本文的文献

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Stereochemistry of Sphingolipids in Ganglioside GM3 Enhances Recovery of Nervous Functionality.神经节苷脂GM3中鞘脂的立体化学增强神经功能的恢复。
ACS Med Chem Lett. 2023 Aug 14;14(9):1237-1241. doi: 10.1021/acsmedchemlett.3c00252. eCollection 2023 Sep 14.