Zhou Wenshu, Wang Cheng, Tan Yige, Lazarovici Philip, Wen Xiaoyan, Li Shaoping, Zheng Wenhua
Faculty of Health Sciences, and Zhuhai UM Science & Technology Research Institute University of Macau Macau SAR China.
State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming China.
Ibrain. 2025 Feb 8;11(1):84-97. doi: 10.1002/ibra.12192. eCollection 2025 Spring.
The aggregation of β-amyloid (Aβ) peptides has been associated with the onset of Alzheimer's disease (AD) by causing neurotoxicity due to oxidative stress and apoptosis. Cordycepin is a natural derivative of the nucleoside adenosine that displays potent antioxidant, antitumor, anti-inflammatory, and neuroprotective properties. However, the mechanism of the neuroprotective effect of cordycepin toward Aβ-induced neurotoxicity, as well as underlying mechanisms, is still unclear. In this study, we found that cordycepin conferred neuroprotection to catecholaminergic PC12 neuronal cell cultures exposed to Aβ-insult by reducing the production of reactive oxygen species, restoring the mitochondrial membrane potential, and inhibiting apoptosis. Cordycepin stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and cyclic AMP-responsive element-binding protein (CREB) in a time- and concentration-dependent manner. Inhibition of the ERK pathway reduced the neuroprotective effect of cordycepin. Similar results were obtained with hippocampal HT22 neuronal cell cultures. Cumulatively, these findings suggest that cordycepin-induced neuroprotection toward Aβ neurotoxic insult may involve activation of the ERK/CREB pathway. This study expands our knowledge of the neuroprotective function of cordycepin and suggests that it holds promise as a natural lead compound for drug development in AD.
β-淀粉样蛋白（Aβ）肽的聚集通过氧化应激和细胞凋亡导致神经毒性，进而与阿尔茨海默病（AD）的发病相关。虫草素是核苷腺苷的天然衍生物，具有强大的抗氧化、抗肿瘤、抗炎和神经保护特性。然而，虫草素对Aβ诱导的神经毒性的神经保护作用机制及其潜在机制仍不清楚。在本研究中，我们发现虫草素通过减少活性氧的产生、恢复线粒体膜电位和抑制细胞凋亡，对暴露于Aβ损伤的儿茶酚胺能PC12神经元细胞培养物具有神经保护作用。虫草素以时间和浓度依赖的方式刺激细胞外信号调节激酶（ERK）和环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化。抑制ERK途径会降低虫草素的神经保护作用。在海马HT22神经元细胞培养物中也获得了类似的结果。总的来说，这些发现表明虫草素诱导的对Aβ神经毒性损伤的神经保护作用可能涉及ERK/CREB途径的激活。本研究扩展了我们对虫草素神经保护功能的认识，并表明它有望成为AD药物开发的天然先导化合物。
