Cao Fanfan, Xu Limin, He Xiaoxue, Chi Yongbin, Wang Ying, Liu Qiuyun, Zhang Denghai
School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai, China.
Shanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Department of Central Laboratory, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
Arch Med Sci. 2024 Jun 12;21(2):538-554. doi: 10.5114/aoms/189906. eCollection 2025.
Alzheimer's disease (AD) is triggered by biological mechanisms such as neuroinflammation and oxidative stress. Endoplasmic reticulum (ER) stress can lead to the expression of molecular chaperones in the ER, which helps in restoring cellular homeostasis. Researchers have highlighted the role of ER stress in the progression of AD, suggesting that regulating it could be a potential treatment strategy for AD.
We induced AD in mice by injecting amyloid beta-peptide 25-35 (Aβ25-35) bilaterally into the CA1 of the dorsal hippocampus. Some mice were administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. The mice underwent the Barnes maze cognitive test and Morris water maze test to assess learning and memory impairment. Levels of interleukin (IL)-1β, tumor necrosis factor α, and IL-10 were measured to evaluate inflammation, while total antioxidant capacity, catalase, malondialdehyde, and superoxide dismutase levels were analyzed to estimate oxidative stress.
Our study showed that pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress. Celastrol also inhibited AD-induced inflammation and oxidative stress. Additionally, celastrol suppressed AD progression by targeting ER stress. These results suggest that celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments.
Celastrol effectively improved learning and memory impairments in AD mice by targeting ER stress-induced inflammation and oxidative stress. This highlights the potential of celastrol as a therapeutic agent for AD.
阿尔茨海默病（AD）由神经炎症和氧化应激等生物学机制引发。内质网（ER）应激可导致内质网中分子伴侣的表达，有助于恢复细胞内稳态。研究人员强调了内质网应激在AD进展中的作用，表明调节内质网应激可能是AD的一种潜在治疗策略。
我们通过双侧向背侧海马体的CA1区注射淀粉样β肽25 - 35（Aβ25 - 35）在小鼠中诱导AD。一些小鼠在注射Aβ25 - 35之前腹腔注射雷公藤红素，而其他小鼠在注射后接受该药物。小鼠接受巴恩斯迷宫认知测试和莫里斯水迷宫测试以评估学习和记忆障碍。测量白细胞介素（IL）-1β、肿瘤坏死因子α和IL-10的水平以评估炎症，同时分析总抗氧化能力、过氧化氢酶、丙二醛和超氧化物歧化酶水平以估计氧化应激。
我们的研究表明，雷公藤红素预处理可通过减轻炎症和氧化应激来预防AD小鼠的学习和记忆衰退。雷公藤红素还抑制AD诱导的炎症和氧化应激。此外，雷公藤红素通过靶向内质网应激抑制AD进展。这些结果表明，雷公藤红素治疗可能有助于解决AD中的学习和记忆缺陷，为潜在的神经保护治疗铺平道路。
雷公藤红素通过靶向内质网应激诱导的炎症和氧化应激有效改善了AD小鼠的学习和记忆障碍。这突出了雷公藤红素作为AD治疗药物的潜力。
