Sirimaharaj Nopdanai, Thiankhaw Kitti, Chattipakorn Nipon, Chattipakorn Siriporn C
Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Mol Neurobiol. 2025 Apr 10. doi: 10.1007/s12035-025-04904-7.
Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder that predominantly affects the elderly. Characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles, AD leads to memory loss, cognitive decline, and severe behavioral changes. As the most common form of dementia, AD imposes a significant global health burden, highlighting the need for interventions that address underlying disease mechanisms rather than only symptomatic treatment. Glial cells, including microglia and astrocytes, play a crucial role in AD progression by mediating neuroinflammatory responses and modulating Aβ clearance and neuronal health. Dysfunction in these cells can exacerbate neuroinflammation and neuronal damage, making glial cells an important target for therapeutic intervention. This review synthesizes findings from in vivo and in vitro studies on melatonin's effects on glial cell dysfunction in AD, emphasizing the multi-mechanistic nature of its neuroprotective properties. Recent studies highlight melatonin's potential as a therapeutic agent that addresses AD-related mechanisms through its interactions with glial cells. Melatonin has demonstrated protective effects, including reducing oxidative stress, apoptosis, and inflammation, inhibiting Aβ fibrillogenesis, and modulating amyloid precursor proteins. Additionally, its influence on glial cell activity, through melatonin receptor pathways, suggests it can alleviate neuroinflammation, a key component of AD progression. The collective evidence points to melatonin's promise as a therapeutic tool with potential roles in both preventive and adjunctive treatments for AD. However, further research is necessary to establish its efficacy and safety in clinical settings.
阿尔茨海默病（AD）是一种主要影响老年人的慢性进行性神经退行性疾病。AD以β淀粉样蛋白（Aβ）斑块和神经原纤维缠结为特征，会导致记忆丧失、认知能力下降和严重的行为改变。作为最常见的痴呆形式，AD给全球健康带来了巨大负担，这凸显了需要采取干预措施来解决潜在的疾病机制，而不仅仅是对症治疗。包括小胶质细胞和星形胶质细胞在内的神经胶质细胞，通过介导神经炎症反应以及调节Aβ清除和神经元健康，在AD进展中发挥关键作用。这些细胞的功能障碍会加剧神经炎症和神经元损伤，使神经胶质细胞成为治疗干预的重要靶点。本综述综合了体内和体外研究中关于褪黑素对AD中神经胶质细胞功能障碍影响的研究结果，强调了其神经保护特性的多机制性质。最近的研究突出了褪黑素作为一种治疗药物的潜力，它通过与神经胶质细胞的相互作用来解决与AD相关的机制。褪黑素已显示出保护作用，包括减少氧化应激、细胞凋亡和炎症，抑制Aβ纤维形成，以及调节淀粉样前体蛋白。此外，其通过褪黑素受体途径对神经胶质细胞活性的影响表明，它可以减轻神经炎症，而神经炎症是AD进展的一个关键因素。总体证据表明褪黑素有望成为一种治疗工具，在AD的预防和辅助治疗中都具有潜在作用。然而，需要进一步研究以确定其在临床环境中的疗效和安全性。
