Parkinson’s disease and brain insulin signaling: Mechanisms and potential role of GLP-1 mimetics

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-05-29 DOI:10.1016/j.brainres.2025.149738

Behina Foroozanmehr , Mohammad Amin Hemmati , Habib Yaribeygi , Sercan Karav , Tannaz Jamialahmadi , Amirhossein Sahebkar

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引用次数: 0

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized primarily by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The pathophysiology of PD is complex and multifactorial involving genetic factors, oxidative stress, mitochondrial dysfunction, impaired protein clearance, and neuroinflammation but recent evidence emphasizes the role of impaired brain insulin signaling. Insulin is a metabolic hormone with extensive effects on metabolic substrates but recent studies have demonstrated that it is also involved in central signaling pathways and induces different brain areas related to food craving, motor activities, cognitive abilities, and emotional feelings. Hence, it has been suggested that induction of brain insulin sensitivity may be a promising treatment for PD. Glucagon-like peptide-1 (GLP-1) mimetics are a new-generation class of antidiabetics that normalize glucose homeostasis via several pathways. Recent studies suggest extra-glycemic benefits for GLP-1 mimetics against PD. GLP-1 mimetics can prevent or slow PD progression. Additionally, these agents can improve cognitive functions by improving brain insulin signaling pathways. In this review, we aim to highlight the role of brain insulin signaling in PD pathophysiology and discuss the possible benefits of GLP-1 mimetics in PD management.

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帕金森病与脑胰岛素信号传导：GLP-1模拟物的机制和潜在作用

帕金森病（PD）是一种常见的神经退行性疾病，其主要特征是黑质致密部多巴胺能神经元的退化。PD的病理生理是复杂的、多因素的，涉及遗传因素、氧化应激、线粒体功能障碍、蛋白质清除受损和神经炎症，但最近的证据强调了脑胰岛素信号受损的作用。胰岛素是一种代谢激素，对代谢底物有广泛的影响，但最近的研究表明，它也参与中枢信号通路，并诱导与食物渴望、运动活动、认知能力和情绪感受相关的不同大脑区域。因此，有人认为，诱导脑胰岛素敏感性可能是一种很有希望的治疗帕金森病的方法。胰高血糖素样肽-1 （GLP-1）模拟物是新一代抗糖尿病药物，通过几种途径使葡萄糖稳态正常化。最近的研究表明，GLP-1模拟物对帕金森病有额外的血糖益处。GLP-1模拟物可以预防或减缓PD的进展。此外，这些药物可以通过改善脑胰岛素信号通路来改善认知功能。在这篇综述中，我们旨在强调脑胰岛素信号在帕金森病病理生理中的作用，并讨论GLP-1模拟物在帕金森病治疗中的可能益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.