固有免疫系统与老年痴呆症（AD）病因网络中相关节点具有直接和间接的联系，如激活的小胶质细胞产生具有神经毒性的炎症细胞因子，后者介导Aβ的生成和聚集、增强AChE和Tau蛋白磷酸化作用，诱发氧自由基生成等，导致AD病变加速。而调节TLRs/MyD88信号通路有可能达到防治AD的目的。本课题依据分子对接和构效关系的研究结果，设计、合成新型的作用于MyD88的化合物，研究其在调节TLRs/MyD88信号传导通路中的作用，对维持Aβ的平衡、减缓Aβ聚集、抑制炎性细胞因子的生成，进而影响AD病因网络中其他相关因素并减缓AD产生和病变加速的作用及作用机制，考察TLRs/MyD88信号通路与AD病因网络的相关性。探索利用作用于TLRs/MyD88信号通路的化合物，达到防治AD产生和病变加速的可行性、作用机制及影响因素，为具有新作用机制的AD防治药物的设计提供理论依据和实验数据。

Innate immune system have direct and indirect relationship with the correlative nodes of Alzheimer`s disease(AD) pathgeny pathway, such as the neurovirulent inflammatory cytokines which have produced by activated microglial cells, could mediate the Aβ create and aggregate, enhance the activity of AChE and the function of Tau protein phosphorylation and induce the production of oxygen radical, finally to induce the neurone apoptosis quickly and generat lesion accelerated of AD. However, adjusting MyD88 via TLRs signal passageway could be attained the perpose of prevent and cure of AD..This item will in accordance with the results of molecular docking and QSAR of non-peptide compounds which acted on MyD88, design and synthesis the new compounds acting on MyD88. Study the function in the field of adjust MyD88 via TLRs signal passageway, and the influnce of maintain Aβ equilibrium, reduce Aβ aggregation and slow down the nerve cell fleetly apoptosis which induced by inflammatory cytokins, then effcted othe relevant factors(targets) of the AD pathogeny pathway. Explore the feasibility, mechanism and influencing factors of prophylaxis and treatment of generation and lesion expedited of AD gutting through adjust innate immune system by using the compounds which act on MyD88, The necessary theoretically gist and basic experiment data for the design of drugs which have new mode of action of prevent and cure of AD will be provided..This item will mainly investigated the correlation of the TLRs/MyD88 signal passageway and the AD pathogeny pathway, studies the compounds is how to adjust Aβ equilibrium in brain, reduce the Aβ aggregation, slow down the nerve cell damage from Aβ and inflammatory cytokins and avoid the lesion expedited of AD by means of MyD88.