二甲双胍与神经退行性变概述:全面综述
Overview of Metformin and Neurodegeneration: A Comprehensive Review.
作者信息
Kruczkowska Weronika, Gałęziewska Julia, Buczek Paulina, Płuciennik Elżbieta, Kciuk Mateusz, Śliwińska Agnieszka
机构信息
Department of Functional Genomics, Faculty of Medicine, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, Poland.
Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland.
出版信息
Pharmaceuticals (Basel). 2025 Mar 28;18(4):486. doi: 10.3390/ph18040486.
This comprehensive review examines the therapeutic potential of metformin, a well-established diabetes medication, in treating neurodegenerative disorders. Originally used as a first-line treatment for type 2 diabetes, recent studies have begun investigating metformin's effects beyond metabolic disorders, particularly its neuroprotective capabilities against conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, and multiple sclerosis. Key findings demonstrate that metformin's neuroprotective effects operate through multiple pathways: AMPK activation enhancing cellular energy metabolism and autophagy; upregulation of antioxidant defenses; suppression of inflammation; inhibition of protein aggregation; and improvement of mitochondrial function. These mechanisms collectively address common pathological features in neurodegeneration and neuroinflammation, including oxidative stress, protein accumulation, and mitochondrial dysfunction. Clinical and preclinical evidence supporting metformin's association with improved cognitive performance, reduced risk of dementia, and modulation of pathological hallmarks of neurodegenerative diseases is critically evaluated. While metformin shows promise as a therapeutic agent, this review emphasizes the need for further investigation to fully understand its mechanisms and optimal therapeutic applications in neurodegenerative diseases.
这篇综述探讨了已被广泛使用的糖尿病药物二甲双胍在治疗神经退行性疾病方面的治疗潜力。二甲双胍最初被用作2型糖尿病的一线治疗药物,最近的研究开始探究其在代谢紊乱之外的作用,特别是其对帕金森病、阿尔茨海默病、亨廷顿病和多发性硬化症等疾病的神经保护能力。主要研究结果表明,二甲双胍的神经保护作用通过多种途径发挥:激活AMPK增强细胞能量代谢和自噬;上调抗氧化防御;抑制炎症;抑制蛋白质聚集;以及改善线粒体功能。这些机制共同解决了神经退行性变和神经炎症中的常见病理特征,包括氧化应激、蛋白质积累和线粒体功能障碍。本文对支持二甲双胍与改善认知功能、降低痴呆风险以及调节神经退行性疾病病理特征相关的临床和临床前证据进行了批判性评估。虽然二甲双胍显示出作为治疗药物的潜力,但本综述强调需要进一步研究,以充分了解其作用机制以及在神经退行性疾病中的最佳治疗应用。