GLP-1受体激动剂在帕金森病疾病修饰治疗中的转化研究进展

Advances in Translational Research on GLP-1 Receptor Agonists for Disease-Modifying Therapy of Parkinson’s Disease

摘要: 帕金森病(PD)是一种常见的神经退行性疾病，现有以多巴胺能药物为主的疗法仅能缓解症状，无法延缓或阻止疾病进展，因此开发有效的疾病修饰疗法是当前临床的迫切需求。近年研究揭示，脑胰岛素抵抗与神经退行性变过程密切相关，为PD治疗提供了新的干预靶点。胰高血糖素样肽-1受体激动剂(Glucagon-Like Peptide-1 Receptor Agonists, GLP-1RAs)作为一类成熟的降糖药物，在大量临床前研究中已显示出显著的神经保护潜力，并已迈入临床转化探索阶段。本综述系统梳理了以艾塞那肽、利司那肽、司美格鲁肽为代表的GLP-1RAs，从动物模型研究到最新临床试验的核心进展，重点分析了其在改善PD患者运动与非运动症状、以及潜在的疾病修饰效应方面的有效性与安全性证据，并深入探讨了当前临床转化过程中面临的关键挑战与未来的研究方向。

Abstract: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder. Current therapies, predominantly relying on dopaminergic agents, offer merely symptomatic relief and fail to delay or halt disease progression; thus, the development of efficacious disease-modifying therapies remains an urgent clinical imperative. Recent studies have elucidated that brain insulin resistance is closely associated with the neurodegenerative process, providing novel therapeutic targets for PD intervention. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), an established class of antidiabetic agents, have demonstrated robust neuroprotective potential in extensive preclinical studies and have subsequently advanced into the exploratory phase of clinical translation. This review systematically delineates the pivotal advancements of representative GLP-1RAs—namely exenatide, lixisenatide, and semaglutide—spanning from animal models to the latest clinical trials. It comprehensively analyzes the evidence regarding their efficacy and safety in ameliorating both motor and non-motor symptoms in PD patients, alongside their potential disease-modifying effects. Furthermore, this review provides an in-depth discussion on the critical challenges currently encountered in clinical translation and outlines future research directions.