Aβ沉积引发的神经炎症反应是阿尔茨海默病(AD)最重要的发病机制之一。RAGE/TLR2/TLR4-NF-κB介导的炎症反应被认为在AD病理过程中起重要作用，但其上游分子HMGB1却未受到足够重视。结合文献报道及前期研究，我们认为：Aβ触发的HMGB1释放可能对RAGE/TLR2/TLR4-NF-κB信号通路的上调起关键作用，姜黄素(传统中药姜黄最主要的活性成分)的抗AD作用可能是通过抑制HMGB1而下调RAGE/TLR2/TLR4-NF-κB信号通路实现的。我们拟采用Aβ损伤细胞及转基因AD小鼠为模型，研究干预HMGB1对RAGE/TLR2/TLR4-NF-κB信号通路的影响；探讨姜黄素是否通过抑制HMGB1影响RAGE/TLR2/TLR4-NF-κB信号通路从而实现其抗AD作用。本项目的顺利实施将为开发针对Aβ神经炎症反应的药物提供思路，也为姜黄素预防AD提供理论与实验依据。

Nerve inflammation reaction caused by Aβ deposition is one of the most important pathogenesis in Alzheimer disease (AD). Inflammatory response mediated by RAGE/TLR2/TLR4-NF-κB signaling pathway is considered to play an important role in the AD pathological process, but its upstream molecule-HMGB1 has not been given adequate attention. Combined literature reports and our preliminary studies, we believe that HMGB1 release triggered by Aβ may play a key role in the increase of RAGE/TLR2/TLR4-NF-κB signaling pathway, and anti-AD role of curcumin (traditional Chinese medicine, turmeric main active ingredient) may be adjusted downwards by inhibiting HMGB1 the RAGE/TLR2/TLR4-NF-κB signaling pathway. We intend to use Aβ damage cells and transgenic AD mice as models to study the impact of intervention HMGB1 on RAGE/TLR2/TLR4-NF-κB signaling pathway, and investigate the anti-AD effects of curcumin whether by inhibiting the HMGB1 from impacting RAGE/TLR2/TLR4-NF-κB signaling pathway or not. The implementation of this project will provide ideas to develop drugs aiming at Aβ nerve inflammation, and also provide theoretical and experimental basis for the prevention of Alzheimer of curcumin.