GLP-1受体激动剂治疗阿尔茨海默病的研究进展
Research Progress of GLP-1 Receptor Agonists in the Treatment of Alzheimer’s Disease
摘要: 胰高血糖素样肽1受体激动剂(Glucagon-like peptide-1 receptor agonists, GLP-1RAs)是一类安全有效的降糖药物，具有外周和中枢的双重作用。随着对该类药物作用机制的深入研究，现已有大量的研究表明GLP-1RAs除了具有良好的降糖效果外，还具有心血管保护作用以及肾脏保护作用，而GLP-1RAs是否具有神经保护作用，则是一个新的探索领域。2型糖尿病(T2DM)作为痴呆的危险因素，已被证实和痴呆之间具有共同的病理生理机制。在人脑中，GLP-1R被发现存在于海马、丘脑、纹状体、杏仁核、下丘脑、颞叶皮质等调控认知功能的中枢及边缘神经系统结构区域，且GLP-1R的表达已被观察到在特定的细胞亚型中对记忆和学习功能有至关重要的影响，大量的动物模型及一些临床研究已经展现了GLP-1RAs潜在的神经保护作用，随着对GLP-1RAs神经保护机制及作用效果的研究，GLP-1RAs或可能成为防治认知障碍的新药物，尽管其确切机制尚未完全确定。在本综述中，我们旨在探讨GLP-1RAs治疗阿尔茨海默症的相关机制，并介绍其目前在临床研究中的相关进展。
Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of safe and effective hypoglycemic agents that exert dual effects on both the peripheral and central nervous systems. With advances in understanding their mechanisms of action, numerous studies have demonstrated that GLP-1RAs not only provide effective glycemic control but also offer cardiovascular and renal protective benefits. The potential neuroprotective effects of GLP-1RAs represent a novel area of investigation. Type 2 diabetes mellitus (T2DM), a known risk factor for dementia, shares common pathophysiological mechanisms with neurodegenerative diseases. In the human brain, GLP-1 receptors (GLP-1Rs) are expressed in central and peripheral nervous system regions involved in cognitive functions, including the hippocampus, thalamus, striatum, amygdala, hypothalamus, and temporal lobe cortex. The expression of GLP-1Rs in specific neuronal subtypes has been shown to play a critical role in memory and learning processes. Numerous animal studies and some clinical trials have demonstrated the potential neuroprotective effects of GLP-1RAs. As research into the neuroprotective mechanisms and effects of GLP-1RAs progresses, these agents may emerge as promising therapeutics for preventing cognitive impairment, although their precise mechanisms remain to be fully elucidated. This review aims to explore the mechanisms by which GLP-1RAs may treat Alzheimer’s disease and to summarize current advances in clinical research.
文章引用：勾琳娜, 李兴升. GLP-1受体激动剂治疗阿尔茨海默病的研究进展[J]. 临床医学进展, 2025, 15(12): 2047-2055. https://doi.org/10.12677/acm.2025.15123625

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