阿尔茨海默病（AD）是一种病因复杂的神经退行性疾病，目前尚无特效药。本课题组前期研究发现，鲨鱼硫酸软骨素的氧化降解产物低分子硫酸软骨素（LMWCS）在体外能够抑制Aβ25-35对PC12和SH-SY5Y细胞的毒性，在体内能够改善脑室注射Aβ1-40引起的小鼠空间记忆障碍，提示LMWCS可能是一种良好的抗阿尔兹海默症的活性多糖。在此课题中我们将进一步研究LMWCS抗AD的途径与机制：利用荧光素和同位素分别标记LMWCS，分别注射和口服给药研究LMWCS的体内分布以确定LMWCS的作用部位；利用转基因小鼠（5XFAD小鼠），通过对其脑和血液中Aβ1-40、Aβ1-42、炎症因子及其他相关因子与蛋白的检测，以及对转基因细胞（SH-SY5Y-APP695）相关指标和蛋白水平的检测，进一步评价LMWCS防治AD的效果与机制。本研究将揭示LMWCS抗AD途径与作用机制。

Alzheimer’s disease (AD) is a neurodegenerative disease with complex pathogenesis. Till now, and there is no desirable medicine against it. In previous research, we found that low molecular weight chondroitin sulfate (LMWCS), which was obtained by oxidative degradation of the chondroitin sulfate (CS) from shark cartilage, could inhibit the neurotoxicity induced by Aβ25-35 on PC12 and SH-SY5Y cells in vitro, and could also improve the space memory disorder of mice induced by intraperitoneal injection of Aβ1-42 in vivo. The results suggest that LMWCS may be a good anti-AD drug candidate. In this research, we will do further research on the path and mechanism of the anti-AD activity of LMWCS. The site of action will be explored by studying the distribution of LMWCS in vivo by injection or oral administration of LMWCS which is labeled by fluorescein and isotopes respectively. In order to further evaluate the anti-AD activity and mechanism of LMWCS, the changes of Aβ1-40 and Aβ1-42 in brain and blood, pre-inflammatory cytokines, and relevant factors and proteins in transgenic mice (5XFAD mice), as well as relevant indexes and factors in transgenic cells (SH-SY5Y-APP695 cell) will be measured. The study will reveal the anti-AD path and mechanism of LMWCS and lay the foundation for the development of LMWCS, which has abundant source, no toxiccity and side effects, and various activities in preventing senile diseases (cardiovascular diseases, osteoarthritis, etc. ), as an anti-AD new drug.