已知细胞内Aβ沉积先于细胞外，是导致AD神经活动异常和细胞凋亡的重要因素。我们前期的研究发现p38MAPK对细胞内化Aβ具有调控作用，在MAPK家族中p38、JNK、ERK1/2都参与了和蛋白质内化相关事件，而后两者是否也参与细胞内化Aβ鲜为人知。本课题探索JNK/ERK1/2对受体介导神经细胞内化Aβ及其作用调控机制。首先采用形态学、RT-PCR、ELISA结合行为学、电生理学等技术观察分析Aβ内化入神经细胞类型、Aβ沉积量，Aβ内化相关受体LRP1、α7nAChR与ERK1/2/JNK信号通路间的关系，同时分析细胞凋亡相关事件、神经突触可塑性、学习记忆力；其次应用免疫共沉淀、RNAi技术结合通路阻断剂分析ERK1/2/JNK对LRP1、α7nACh介导神经细胞内化Aβ及其作用影响，阐明JNK/ERK1/2对神经细胞内化Aβ及其作用调控机制，为揭示AD发病机制及AD治疗提供新思路和靶点。

It has been known that intracellular deposition of beta amyloid protein (Aβ) is earlier than extracellular one, and an important factor of abnormal neural activity and apoptosis in Alzheimer’s disease (AD). MAPK signal transduction pathways is activated in AD. Our previous study found that p38MAPK has a role in the regulation of internalization of Aβ. The MAPK signal transduction pathway including three subfamilies p38 MAPK, JNK and ERK1/2 all are involved in the internalization of protein related events. However, whether JNK and ERK1/2 signal transduction pathways are also involved in the regulation of the receptor-mediated internalization of Aβ and its effects is little-known already. This study will be on the basis of previous work, focus on the regulation of JNK/ERK1/2 signal transduction pathway on the receptor-mediated internalization of Aβ and its effects in neuron. First of all, using morphological method, RT-PCR, ELISA combined with behavioral, electrophysiological (MED planar microelectrode array record LTP/LTD) technology to observe and analyze the Aβ internalized into neural cell types, the quantity of Aβ deposition, the relationship between the expression of low-density lipoprotein receptor-related protein-1(LRP1), alpha 7 nicotinic acetylcholine receptor (α7nAChR ) and JNK/ ERK1/2 signal transduction pathway. Meanwhile, to analysis apoptotic related events, the changes of synaptic plasticity and learning and memory in mice. Secondly, the immunoprecipitation, siRNA and inhibitor of JNK/ERK1/2 are emploied to investigate the effects of JNK/ERK1/2 signal transduction pathway on the regulation of the internalization of Aβ and its effects and verify the related receptor mediated internalization of Aβ. To elucidate the regulation of the internalization of Aβ and its effects by JNK/ERK1/2 signal transduction pathway and reveal the pathogenesis of AD, and provide new ideas and targets for the treatment of AD.