关键词: 氧化应激, α2,6-唾液酸乳糖, 噬菌体展示, 模拟肽, 小脑颗粒神经元, 中枢神经系统, 接骨木凝集素, 神经元存活, 神经突向外生长, 神经元发生, 神经退行性疾病

Abstract: 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 α2,6-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 H2O2-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.

Key words: 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