脂联素对阿尔茨海默症的神经保护作用及其机制研究

项目名称： 脂联素对阿尔茨海默症的神经保护作用及其机制研究

项目编号： No.81500930

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 闫海静

作者单位： 滨州医学院

项目金额： 17.5万元

中文摘要： 阿尔茨海默症（AD）是一种中枢神经系统退行性疾病，主要临床表现为进行性记忆减退和认知障碍，其病因和发病机制仍不明确。特征性神经病理改变为细胞外老年斑、细胞内神经原纤维缠结形成以及神经元丢失。脂联素(APN)是由脂肪细胞分泌的一种蛋白类激素，能通过血脑屏障，在神经系统发挥重要作用。我们前期研究表明脂联素有神经保护和神经再生活性。在AD患者体内，血清脂联素水平显著降低。脂联素受体AdipoR1和AdipoR2下游效应分子p38-MAPK/GSK3β、AMPK和mTOR与AD发病机制和病理变化密切相关。本项目利用三重转基因AD小鼠(3xTg-AD)模型，研究脂联素对AD认知功能减退、神经病理变化的影响。拟利用APN-/-、AdipoR1-/-、AdipoR2-/-小鼠研究脂联素如何通过特异受体激活下游信号通路影响AD神经病理变化及认知功能减退进程，为AD发病机制和临床治疗提供新的思路和理论基础。

中文关键词： 阿尔茨海默症；脂联素；脂联素受体；MAPK；AMPK/mTOR

英文摘要： Alzheimer's disease (AD) is a common neurodegenerative disease, which is clinically characterized by cognitive decline with loss of memory. Neuropathological alterations include extracellular deposition of beta amyloid-Aβ and intracellular accumulation of tau protein, which are the main component of senile plaques and neurofibrillary tangles. Adiponectin is a protein hormone secreted by fat cells; it can cross the blood-brain-barrier and exert its biological effects in the brain. Our research has shown that adiponectin has neuroprotective effects and promotes neurogenesis. In AD patients, a decline in plasma adiponectin level is correlated with the severity of the disease. Moreover, the signaling pathways that lie downstream of adiponectin receptors AdipoR1 and AdipoR2, including p38-MAPK/GSK3β, AMPK and mTOR, are involved in the neuropathological changes of AD. By applying the triple transgenic mice 3xTg-AD, we will study the effects of adiponectin on AD induced cognition impairment and pathological changes. The proposed studies will use APN-/-、AdipoR1-/-、AdipoR1-/- mice to determine the effects and mechanisms of adiponectin in 3xTg-AD mouse model and further to identify the signaling pathways underlying neuropathologies and cognitive deficits.

英文关键词： Alzheimer’s disease;adiponectin;adiponectin receptors;MAPK;AMPK/mTOR