A mimetic peptide of α2,6-sialyllactose promotes neuritogenesis  

作　　者：Shuang-Xi Chen Jia-Hui He Yong-Jian Mi Hui-Fan Shen Melitta Schachner Wei-Jiang Zhao 

机构地区：[1]Center for Neuroscience,Shantou University Medical College,Shantou,Guangdong Province,China [2]Department of Neurology,The First Affiliated Hospital of University of South China,Hengyang,Hunan Province,China [3]Department of Neurology,Chongqing Qijiang Renmin Hospital,Chongqing,China [4]Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience,Rutgers University,Piscataway,NJ,USA

出　　处：《Neural Regeneration Research》2020年第6期1058-1065,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81471279 and No.81171138(to WJZ);Talent Support Grant from Shantou University Medical College,China,No.2501220118(to WJZ);the Li Kashing Foundation,No.LD030302(to MS)

摘　　要：Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose（6’-SL）,which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6’-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6’-SL binding to the lectin.Indeed,lectin binding to 6’-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6’-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H202-induced oxidative stress.The combined results indicate that the 6’-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China（approval No.SUMC 2014-004） on February 20,2014.

关 键 词：central nervous system CEREBELLAR granule neurons MIMETIC peptide neural cell adhesion molecule L1 NEURITOGENESIS NEURODEGENERATIVE disease neuronal survival oxidative stress PHAGE display SAMBUCUS nigra lectin α2 6-sialyllactose 

分 类 号：R[医药卫生]