Sobell Department of Motor Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom.
Sobell Department of Motor Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom.
Neuropharmacology. 2018 Jul 1;136(Pt B):260-270. doi: 10.1016/j.neuropharm.2017.09.023. Epub 2017 Sep 18.
There is increasing interest in the potential role of glucagon-like peptide-1 (GLP-1) receptor agonists as neuroprotective treatments in neurodegenerative diseases including Parkinson's disease following the publication of the results of the Exenatide-PD trial. Of the current GLP-1 receptor agonists already licensed to treat Type 2 diabetes several including exenatide, liraglutide and lixisenatide are the subject of ongoing clinical trials in PD. The underlying rationale for using drugs licensed and effective for T2DM in PD patients therefore needs to be scrutinized, and the results obtained to date critically reviewed. We review the relationship between insulin resistance and Parkinson's disease, the implications on pathogenesis and the efforts to reposition GLP-1 agonists as potential treatments for Parkinson's disease and give an overview of the pre-clinical and clinical data supporting the use of exenatide in Parkinson's disease with a discussion regarding possible mechanisms of action. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
人们对胰高血糖素样肽-1（GLP-1）受体激动剂在神经退行性疾病（包括帕金森病）中的神经保护作用越来越感兴趣，这是在 Exenatide-PD 试验的结果公布之后。目前已经获得许可用于治疗 2 型糖尿病的几种 GLP-1 受体激动剂，包括 exenatide、liraglutide 和 lixisenatide，正在进行 PD 的临床试验。因此，需要仔细审查在 PD 患者中使用已获得许可且对 T2DM 有效的药物的基本原理，并批判性地审查迄今为止获得的结果。我们回顾了胰岛素抵抗与帕金森病之间的关系，对发病机制的影响，以及将 GLP-1 激动剂重新定位为帕金森病潜在治疗方法的努力，并概述了支持 exenatide 在帕金森病中应用的临床前和临床数据，并讨论了可能的作用机制。本文是特刊“代谢障碍作为神经退行性疾病的危险因素”的一部分。
