Title | Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety |
Author | |
Corresponding Author | Jiang,Faqin; Yang,Guangyu |
Publication Years | 2022-11-05
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DOI | |
Source Title | |
ISSN | 0223-5234
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EISSN | 1768-3254
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Volume | 241 |
Abstract | Ganglioside GM1 is a glycosphingolipid found on mammalian cell membranes, and it is involved in ischemic encephalopathy, spinal cord injury and neurodegenerative diseases. Fatty acids, as a structure module of GM1, have been reported to affect its physiological function and neurite growth activity. Due to the limitation of preparation methods, the function of GM1 derivatives containing different fatty acids in nerve cells has not been systematically studied. To discover novel GM1 derivatives as nerve growth-promoting agents, we developed an efficient SA_SCDase enzymatic synthetic system of GM1 derivatives, yielding twenty GM1 derivatives with unsaturated fatty acid chains in high total yields (16–67%). Subsequently, the neurite outgrowth activities of GM1 derivatives were assessed on Neuro2a Cells. Among all the GM1 derivatives, GM1 (d18:1/C16:1) induced demonstrably neurite outgrowth activity. The subsequent RNA-sequencing (RNA-seq) and Western blot analysis was then performed and indicated that the mechanism of nerve cells growth involved cholesterol biosynthesis regulation by up-regulating SREBP2 expression or ERBB4 phosphorylation to activate the PI3K-mTOR pathway. |
Keywords | |
URL | [Source Record] |
Indexed By | |
Language | English
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SUSTech Authorship | Others
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Funding Project | National Natural Science Foundation of China[32030063];
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WOS Research Area | Pharmacology & Pharmacy
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WOS Subject | Chemistry, Medicinal
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WOS Accession No | WOS:000888443500004
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Publisher | |
ESI Research Field | CHEMISTRY
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Scopus EID | 2-s2.0-85135699687
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Data Source | Scopus
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Citation statistics |
Cited Times [WOS]:3
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Document Type | Journal Article |
Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/382321 |
Department | School of Medicine |
Affiliation | 1.State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai,200240,China 2.School of Pharmacy,Shanghai Jiao Tong University,Shanghai,200240,China 3.Glycogene. LLC,Wuhan Precision Medicine Industrial Base,East Lake New Technology Development Zone,Wuhan,10th Floor, Building 3, Gaokeyuan Road,430074,China 4.School of Medicine,Southern University of Science and Technology,518055,China |
Recommended Citation GB/T 7714 |
Chen,Xiaohui,Jin,Xuefeng,Huang,Fengtao,et al. Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,241.
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APA |
Chen,Xiaohui.,Jin,Xuefeng.,Huang,Fengtao.,Wang,Juntao.,Cao,Xuefeng.,...&Yang,Guangyu.(2022).Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,241.
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MLA |
Chen,Xiaohui,et al."Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 241(2022).
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