In Alzheimer’s disease (AD), β-amyloid (Aβ) protein toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and cell death. Cordycepin is a derivative of the nucleoside adenosine; also, it is speculated to exert neuroprotective effects against Aβ-induced oxidative toxicity in hippocampal neurons. In the present study, the fluorescence detection method and whole-cell patch-clamp recordings were used to study the neuroprotective effects against Aβ-induced toxicity in the primary hippocampal cultured neurons. The results revealed that Aβ_25–35 toxicity causes increased cellular ROS production and abnormal calcium homeostasis in hippocampal neurons. Moreover, Aβ_25–35-induced cytotoxicity led to a series of downstream events, including the activation of acetylcholinesterase, increased p-Tau expression, and increased apoptosis. Cordycepin inhibits ROS production, elevated levels of Ca²⁺ induced by Aβ_25–35, and the activation of acetylcholinesterase; all these are involved in oxidative-induced apoptosis. In addition, it decreases the increased p-Tau expression that plays a key role in the initiation of the AD. Results showed that the anti-apoptotic effects of cordycepin are partially dependent on the activation of adenosine A₁ receptor, whereas an antagonist selectively attenuated the neuroprotective effects of cordycepin. Collectively, these results suggest that cordycepin could be a potential future therapeutic agent for neuronal disorders, such as AD.

在阿尔茨海默氏病（AD）中，β-淀粉样蛋白（Aβ）的蛋白质毒性会增加活性氧（ROS）和细胞内钙水平的形成，从而导致神经元功能障碍，神经退行性疾病和细胞死亡。虫草素是核苷腺苷的衍生物。另外，据推测对海马神经元中Aβ诱导的氧化毒性具有神经保护作用。在本研究中，荧光检测方法和全细胞膜片钳记录用于研究对原代海马培养的神经元中Aβ诱导的毒性的神经保护作用。结果表明，_Aβ25–35毒性导致海马神经元细胞ROS产生增加和钙稳态异常。此外，_Aβ25–35诱导的细胞毒性导致一系列下游事件，包括乙酰胆碱酯酶的激活，p-Tau表达增加和细胞凋亡增加。虫草素抑制ROS的产生，钙水平升高²⁺ Aβ引起_25-35，和乙酰胆碱酯酶的活化; 所有这些都与氧化诱导的细胞凋亡有关。另外，它降低了增加的p-Tau表达，其在AD的起始中起关键作用。结果表明，虫草素的抗凋亡作用部分取决于腺苷A ₁的活化。受体，而拮抗剂选择性地减弱了虫草素的神经保护作用。总体而言，这些结果表明虫草素可能是神经元疾病（例如AD）的潜在未来治疗剂。