Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao 028000, China.
Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao 028000, China.
Molecules. 2022 Aug 8;27(15):5035. doi: 10.3390/molecules27155035.
Alzheimer's disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.
阿尔茨海默病（AD）是一种主要的神经退行性疾病，但迄今为止，只能对症治疗，而不能改变疾病进程。最近，三唑类及其衍生物已被证明具有治疗 AD 的潜力。在这项研究中，我们从体外和体内两个方面探讨了 4-(4-(庚氧基)苯基)-2,4-二氢-3-1,2,4-三唑-3-酮（W112）对β-淀粉样蛋白（Aβ）诱导的 AD 病理学的神经保护作用及其可能的机制。结果表明，W112 对 Aβ诱导的 PC12 细胞毒性具有神经保护作用，并改善了 Aβ诱导的 AD 样大鼠的学习和记忆能力。此外，蛋白表达测定表明，W112 逆转了 tau 的过度磷酸化，并减少了促炎细胞因子肿瘤坏死因子-α和白细胞介素-6的产生，这在体外和体内研究中均得到证实。进一步的研究表明，丝裂原活化蛋白激酶/核因子-κB 通路的调节在介导 W112 对 AD 样病理学的神经保护作用中起着关键作用。W112 可能成为一种有潜力的 AD 干预药物。
