APP N端片段的神经营养作用

NEUROTROPHIC EFFECT OF APP N-TERMINUS FRAGMENTS

APP是β-淀粉样肽的前体蛋白,由695-770个氨基酸组成,其N端水解产物可分泌至细胞外环境。APP具有促进神经细胞生长作用,其中319-335肽段即APP17肽能提高动物的学习记忆能力,其他APP片段是否具有神经营养功能未见报道。本研究通过观察APPN端片段对人神经母细胞瘤株SY5Y生长的影响以及对实验性糖尿病动物行为的影响,希望发现APP促进神经细胞生长的其他肽段。用化学合成APP N端多肽片段,以SY5Y细胞MTT代谢率、细胞计数、LDH漏出率和实验性糖尿病小鼠水迷宫试验结果为观察指标。结果APP64肽、29肽、11肽均有促进SY5Y细胞生长的作用,APP11肽可提高糖尿病动物水迷宫测试成绩。说明可溶性APP的N端可能具有神经营养作用,我们认为保持此作用的最短片段为APP11肽,此肽段的发现为进一步研究APP的构效关系奠定了基础。

APP is the precursor protein of beta amyloid peptide and composed of 695 - 770 amino acid residues with a soluble N terminus normally. It can enhance neuronal growth. APP 17 peptide which consists of APP 319 - 335 aminoacid sequence, can improve learning and memory abilities, but it has not been reported whether other peptide fragments of APP has neu-rotrophic properties. By observing the effects of APP N-terminus fragments on the growth of SY5Y neuroblastoma cells, and on the behaviour of experimental diabetic animals, this study aims to find other APP fragments that may have neurotrophic actions.Chemically synthesized APP N-terminus fragments were used; MIT metabolic rate of SY5Y cells,cells account, LDH leakage rate,and performance of diabetic mice in the water maze test were taken as indicators. Our results show APP 64 pep-tide,29 peptide and 11 peptide all showed effects in stimulating SY5Y cell growth,and improving performance of animals in the water maze test. The conclusions is that the neurotrophic action of soluble APP is lodged at the N terminus; APP 11 peptide is the shortest fragment that can preserve the neurotrophic action. This discovery will help towards further unraveling the structure-functioin relationship of APP.