Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211166, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211166, China.
Cells. 2023 Sep 25;12(19):2348. doi: 10.3390/cells12192348.
Alzheimer's disease (AD), an age-related degenerative disorder, is characterized by β-amyloid deposition, abnormal phosphorylation of tau proteins, synaptic dysfunction, neuroinflammation, and oxidative stress. Despite extensive research, there are no medications or therapeutic interventions to completely treat and reverse AD. Herein, we explore the potential of hydrocortisone (HC), a natural and endogenous glucocorticoid known to have potent anti-inflammatory properties, in an Aβ-induced AD mouse model. Our investigation highlights the beneficial effects of HC administration on cognitive impairment, synaptic function enhancement, and neuronal protection in Aβ-induced AD mice. Notably, HC treatment effectively suppresses the hyperactivation of microglia and astrocytes, leading to a reduction in proinflammatory factors and alleviation of neuroinflammation. Furthermore, HC intervention demonstrates the capacity to mitigate the generation of ROS and oxidative stress. These compelling findings underscore the potential therapeutic application of HC in AD and present promising opportunities for its utilization in AD prevention and treatment. The implications drawn from our findings indicate that hydrocortisone holds promise as a viable candidate for adjunctive use with other anti-AD drugs for the clinical management of patients presenting with moderate to severe AD.
阿尔茨海默病（AD）是一种与年龄相关的退行性疾病，其特征是β-淀粉样蛋白沉积、tau 蛋白异常磷酸化、突触功能障碍、神经炎症和氧化应激。尽管进行了广泛的研究，但目前尚无药物或治疗干预措施可以完全治疗和逆转 AD。在此，我们研究了氢化可的松（HC）在 Aβ诱导的 AD 小鼠模型中的潜在作用。HC 是一种天然内源性糖皮质激素，具有很强的抗炎特性。我们的研究强调了 HC 给药对 Aβ诱导的 AD 小鼠认知障碍、突触功能增强和神经元保护的有益作用。值得注意的是，HC 治疗可有效抑制小胶质细胞和星形胶质细胞的过度激活，从而减少促炎因子并减轻神经炎症。此外，HC 干预可减轻 ROS 和氧化应激的产生。这些令人信服的发现强调了 HC 在 AD 中的潜在治疗应用，并为其在 AD 的预防和治疗中的应用提供了有前景的机会。我们的研究结果表明，氢化可的松作为其他抗 AD 药物联合使用的辅助药物，有望用于治疗中度至重度 AD 患者。
