Zhang Zefan, Xue Pei, Bendlin Barbara B, Zetterberg Henrik, De Felice Fernanda, Tan Xiao, Benedict Christian
Department of Big Data in Health Science, Zhejiang University School of Public Health and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China.
Mol Psychiatry. 2025 Jan;30(1):237-250. doi: 10.1038/s41380-024-02691-6. Epub 2024 Aug 11.
In the context of the escalating global health challenge posed by Alzheimer's disease (AD), this comprehensive review considers the potential of melatonin in both preventive and therapeutic capacities. As a naturally occurring hormone and robust antioxidant, accumulating evidence suggests melatonin is a compelling candidate to consider in the context of AD-related pathologies. The review considers several mechanisms, including potential effects on amyloid-beta and pathologic tau burden, antioxidant defense, immune modulation, and regulation of circadian rhythms. Despite its promise, several gaps need to be addressed prior to clinical translation. These include conducting additional randomized clinical trials in patients with or at risk for AD dementia, determining optimal dosage and timing, and further determining potential side effects, particularly of long-term use. This review consolidates existing knowledge, identifies gaps, and suggests directions for future research to better understand the potential of melatonin for neuroprotection and disease mitigation within the landscape of AD.
在阿尔茨海默病（AD）对全球健康构成的挑战不断升级的背景下，本综述全面探讨了褪黑素在预防和治疗方面的潜力。作为一种天然存在的激素和强大的抗氧化剂，越来越多的证据表明，褪黑素是与AD相关病理情况下值得考虑的有力候选物。该综述探讨了几种机制，包括对β-淀粉样蛋白和病理性tau蛋白负荷的潜在影响、抗氧化防御、免疫调节以及昼夜节律调节。尽管褪黑素前景广阔，但在临床转化之前仍有几个问题需要解决。这些问题包括对AD痴呆患者或有患AD痴呆风险的患者开展更多随机临床试验、确定最佳剂量和给药时间，以及进一步确定潜在的副作用，尤其是长期使用的副作用。本综述整合了现有知识，找出了差距，并为未来研究提出了方向，以便在AD领域更好地理解褪黑素的神经保护和疾病缓解潜力。
