Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Changchun Street 45, Xicheng District, Beijing, People's Republic of China, 100053.
Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, People's Republic of China.
Mol Neurobiol. 2022 Jun;59(6):3370-3381. doi: 10.1007/s12035-022-02777-8. Epub 2022 Mar 19.
Alzheimer's disease (AD) is the most common form of neurodegenerative disease and most anti-AD drugs have failed in clinical trials; hence, it is urgent to find potentially effective drugs against AD. DL-3-n-butylphthalide (NBP) is a compound extracted from celery seed and is a multiple-target drug. Several studies have demonstrated the neuroprotective effects of NBP on cognitive impairment, but the mechanisms of NBP remains relatively unexplored. In this study, we found that NBP could alleviated the increase of intracellular Ca and reversed down-regulation of Ca/calmodulin-dependent protein kinase alpha (CaMKIIα) signaling and rescued neuronal apoptosis in SH-SY5Y cells treated by Aβ oligomers. However, these neuroprotective effects of NBP on neuronal damage and CaMKIIα signaling were abolished when CaMKIIα expression was knocked down or its activity was inhibited. Thus, our findings suggested that CaMKIIα signaling was required for the neuroprotective effects of NBP in AD and provided an improved basis for elucidating the mechanism and treatment of NBP in AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病，大多数抗 AD 药物在临床试验中都失败了；因此，迫切需要寻找针对 AD 的潜在有效药物。DL-3-正丁基苯酞（NBP）是从芹菜籽中提取的一种化合物，是一种多靶点药物。多项研究表明 NBP 对认知障碍具有神经保护作用，但 NBP 的作用机制仍相对未知。在这项研究中，我们发现 NBP 可以减轻细胞内 Ca 的增加，并逆转 Aβ寡聚体处理的 SH-SY5Y 细胞中 Ca/钙调蛋白依赖性蛋白激酶 α（CaMKIIα）信号的下调，挽救神经元凋亡。然而，当 CaMKIIα 表达被敲低或其活性被抑制时，NBP 对神经元损伤和 CaMKIIα 信号的这些神经保护作用被消除。因此，我们的研究结果表明，CaMKIIα 信号通路是 NBP 治疗 AD 中神经保护作用所必需的，为阐明 NBP 在 AD 中的作用机制和治疗提供了更好的基础。
