Inflammatory response through interleukin-1β (IL-1β) plays a key role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanism of pro-IL-1β processing in AD is not clearly defined. The current study was designed to investigate which of the inflammasome complexes are critical for IL-1β production in AD. An experimental model for Alzheimer like disease was induced in male Wistar rats and Morris Water Maze was used to evaluate the function of learning and memory. The expression of genes involved in inflammasome complex including NLRP1, NLRP3, NLRC4, AIM2, ASC, IL18, IL-1β and caspase-1 was determined via Real-time PCR. Hematoxylin and Eosin (H&E) staining and Immunohistochemistry (IHC) for CD45 was applied to assess inflammatory cells infiltration. Furthermore, caspase-1, IL-1β and phosphorylated tau (p-Tau) protein expressing cells were investigated in the lesion area using immunofluorescence staining technique. The behavioral study revealed that streptozotocin (STZ) injection significantly impaired learning and memory function. In addition, the infiltration of inflammatory cells was confirmed in the hippocampus region of STZ-treated animals. Furthermore, a significant increase in the expression level of NLRC4 inflammasome, ASC and IL-1β was identified in STZ-treated animals. In contrast, no significant difference was observed in other inflammasome components including NLRP1, NLRP3, AIM2, IL-18 and caspase-1 in STZ-treated group compared with the control group. Moreover, the number of caspase-1, IL-1β and p-Tau protein positive cells were remarkably increased in STZ-treated animals. Based on the obtained results, it can be concluded that increased production of IL-1β, caspase-1 and p-Tau through association with NLRC4 inflammasome may be involved in neuroinflammation and memory impairment in AD, which creates a new horizon in this regard. Hence, strategies targeting NLRC4 inflammasome could be beneficial for the treatment of AD.

中文翻译：

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通过caspase-1和IL-1β参与NLRC4炎性体增加了神经发炎，并在阿尔茨海默氏样病的实验模型中导致了记忆障碍。

通过白介素-1β（IL-1β）引起的炎症反应在阿尔茨海默氏病（AD）的发病机理中起着关键作用。但是，尚不清楚AD中pro-IL-1β加工的分子机制。当前的研究旨在调查哪种炎症小体复合物对于AD中IL-1β的产生至关重要。在雄性Wistar大鼠中建立了针对Alzheimer样疾病的实验模型，并使用Morris Water Maze评估学习和记忆功能。通过实时PCR确定涉及炎性体复合物的基因的表达，包括NLRP1，NLRP3，NLRC4，AIM2，ASC，IL18，IL-1β和caspase-1。将苏木精和曙红（H＆E）染色和CD45的免疫组织化学（IHC）用于评估炎症细胞浸润。此外，caspase-1 使用免疫荧光染色技术在病变区域研究了IL-1β和磷酸化tau（p-Tau）蛋白表达细胞。行为研究表明，链脲佐菌素（STZ）注射会严重损害学习和记忆功能。另外，在经STZ处理的动物的海马区中证实了炎性细胞的浸润。此外，在经STZ处理的动物中，NLRC4炎性小体，ASC和IL-1β的表达水平显着增加。相反，与对照组相比，STZ治疗组的其他炎性体成分包括NLRP1，NLRP3，AIM2，IL-18和caspase-1均未观察到显着差异。此外，在STZ处理的动物中，caspase-1，IL-1β和p-Tau蛋白阳性细胞的数量显着增加。根据获得的结果，可以得出结论，通过与NLRC4炎性小体结合而增加IL-1β，caspase-1和p-Tau的产生可能与AD的神经炎症和记忆障碍有关，这在这方面开辟了新的视野。因此，针对NLRC4炎性小体的策略可能对AD的治疗有益。