Liao Wang, Xu Jiaxin, Li Bo, Ruan Yuting, Li Tian, Liu Jun
Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Front Pharmacol. 2022 Jan 27;12:728315. doi: 10.3389/fphar.2021.728315. eCollection 2021.
Alzheimer's disease (AD) is a prevalent neurodegenerative disease predominantly affecting millions of elderly people. To date, no effective therapy has been identified to reverse the progression of AD. Metformin, as a first-line medication for Type 2 Diabetes Mellitus (T2DM), exerts multiple beneficial effects on various neurodegenerative disorders, including AD. Evidence from clinical studies has demonstrated that metformin use contributes to a lower risk of developing AD and better cognitive performance, which might be modified by interactors such as diabetic status and APOE-ε4 status. Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-β (Aβ) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction. Current evidence remains ambiguous and even conflicting. Herein, we review the current state of knowledge concerning the mechanisms of metformin in AD pathology while summarizing current evidence from clinical studies.
阿尔茨海默病（AD）是一种普遍存在的神经退行性疾病，主要影响着数百万老年人。迄今为止，尚未发现有效的治疗方法来逆转AD的进展。二甲双胍作为2型糖尿病（T2DM）的一线用药，对包括AD在内的各种神经退行性疾病具有多种有益作用。临床研究证据表明，使用二甲双胍有助于降低患AD的风险并改善认知表现，而这可能会受到糖尿病状态和载脂蛋白E-ε4状态等相互作用因素的影响。以往的机制研究逐渐揭示了二甲双胍对AD病理和病理生理学的影响，包括神经元丢失、神经功能障碍、淀粉样β蛋白（Aβ）沉积、tau蛋白磷酸化、慢性神经炎症、胰岛素抵抗、葡萄糖代谢受损和线粒体功能障碍。目前的证据仍然不明确甚至相互矛盾。在此，我们回顾了关于二甲双胍在AD病理机制方面的现有知识状态，同时总结了临床研究的当前证据。
