JNK调控的自噬对Aβ聚集的影响及其机制

The abnormal aggregation of β- amyloid（Aβ） in Alzheimer's disease（AD） is a key event。The evidence shows that autophagy is involved in the production and removal of Aβ。The function of autophagy decreased with aging, resulting in the abnormal aggregation of Aβ。The JNK pathway is an important stress protein in the human body, the extracellular signal transferred to cells involved in many physiological and pathological response。A lot of evidence showed that JNK is involved in the formation of Aβ, and closely related to the autophagy .Our recent studies showed that JNK inhibitor SP600125 can significantly reduced the accumulation Aβ and inflammatory reaction in cortex and hippocampus, and improve behavioral and cognitive disorders in AD transgenic mice. But the effect of JNK mediated autophagy of Aβ is unclear. This study intends to use AD transgenic mouse model, using immunohistochemistry, molecular biology, transmission electron microscopy (TEM) methods and technologies, to observe the effect and related mechanism of JNK mediated autophagy on Aβ formation, may provide a new potential therapeutic targets for AD, which has an important science and application prospects

β-淀粉样蛋白（β-amyloid，Aβ）异常聚集是阿尔茨海默病（Alzheimer's disease，AD），发生的一个关键性事件。证据表明，自噬参与了Aβ的产生和清除。人体自噬功能随年龄增长而减弱，导致Aβ异常聚集，引发AD。JNK通路是人体重要的应激反应蛋白，其将细胞外信号转送到细胞内，参与多种生理与病理反应。大量证据表明，JNK也参与了Aβ的形成过程，其与细胞自噬关系密切。我们新近研究发现，JNK阻断剂SP600125治疗能明显减轻AD转基因小鼠皮层和海马Aβ的积聚及炎症反应，改善AD转基因小鼠的行为学及认知障碍，但是JNK介导的自噬对Aβ的影响目前尚不清楚。本研究拟利用AD转基因小鼠模型，采用免疫组织化学、分子生物学、透射电镜等多种方法和技术，观察JNK介导的自噬对Aβ形成的影响及相关机制，可能为AD提供新的潜在的治疗靶点，有重要的科学价值及应用前景。