Alzheimer's disease (AD) is one of the most common age-related neurodegenerative diseases and the most devastating form of senile dementia. It has a complex mechanism and no effective treatment. Exploring the pathogenesis of AD and providing ideas for treatment can effectively improve the prognosis of AD. Microglia were incubated with β-amyloid protein 1-42 (Aβ1-42) to construct an AD cell model. After microglia were activated, cell morphology changed, the expression level of inflammatory factors increased, cell apoptosis was promoted, and the expression of microtubule-associated protein (Tau protein) and related proteins increased. By up-regulating and down-regulating Toll-like receptor 4 (TLR4), the cells were divided into TLR4 knockdown negative control group(Lv-NC group), TLR4 knockdown group(Lv-TLR4 group), TLR4 overexpression negative control group(Sh-NC group), and TLR4 overexpression group(Sh-TLR4 group). The expression of inflammatory factors was detected again. It was found that compared with the Lv-NC group, the expression of various inflammatory factors in the Lv-TLR4 group decreased, cell apoptosis was inhibited, and the expression of Tau protein and related proteins decreased. Compared with the Sh-NC group, the expression of inflammatory factors in the Sh-TLR4 group increased, cell apoptosis was promoted, and the expression of Tau protein and related proteins increased. These results indicate that Aβ1-42 may promote microglial activation and apoptosis by binding to TLR4. Reducing the expression of TLR4 can reduce the occurrence of inflammatory response in AD cells and slow down cell apoptosis. Therefore, TLR4 is expected to become a new target for the prevention and treatment of AD.

中文翻译：

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Aβ1-42 通过与 TLR4 结合促进 AD 进展中的小胶质细胞活化和细胞凋亡


阿尔茨海默病 （AD） 是最常见的与年龄相关的神经退行性疾病之一，也是最具破坏性的老年痴呆形式。它的作用机制复杂，没有有效的治疗方法。探讨 AD 的发病机制，为治疗提供思路，可有效改善 AD 的预后。将小胶质细胞与 β-淀粉样蛋白 1-42 （Aβ1-42） 孵育，构建 AD 细胞模型。小胶质细胞活化后，细胞形态发生变化，炎症因子表达水平升高，细胞凋亡得到促进，微管相关蛋白 （Tau 蛋白） 和相关蛋白的表达增加。通过上调和下调Toll样受体4（TLR4），将细胞分为TLR4敲低阴性对照组（Lv-NC组）、TLR4敲低组（Lv-TLR4组）、TLR4过表达阴性对照组（Sh-NC组）和TLR4过表达组（Sh-TLR4组）。再次检测炎症因子的表达。结果发现，与 Lv-NC 组相比，Lv-TLR4 组各种炎症因子的表达降低，细胞凋亡受到抑制，Tau 蛋白和相关蛋白的表达降低。与 Sh-NC 组相比，Sh-TLR4 组炎症因子表达升高，细胞凋亡得到促进，Tau 蛋白及相关蛋白表达升高。这些结果表明，Aβ1-42 可能通过与 TLR4 结合促进小胶质细胞活化和细胞凋亡。降低 TLR4 的表达可以减少 AD 细胞炎症反应的发生并减缓细胞凋亡。因此，TLR4 有望成为预防和治疗 AD 的新靶点。