Role of Glucagon-Like Peptide-1 on Amyloid, Tau, and α-Synuclein: Target Engagement and Rationale for the Development in Neurodegenerative Disorders

IF 7.5 1区医学 Q1 BEHAVIORAL SCIENCES

Neuroscience and Biobehavioral Reviews Pub Date : 2025-04-17 DOI:10.1016/j.neubiorev.2025.106159

Hezekiah C.T. Au , Pak Ho Lam , Poh Khuen Lim , Roger S. McIntyre

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引用次数: 0

Abstract

Introduction

Glucagon-like Peptide-1 (GLP-1) and Glucagon-Like Peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroprotective effects in neurodegenerative disorders. We conducted a comprehensive synthesis of known effects of GLP-1 and GLP-1 RAs on the cognitive, cellular, and molecular changes in neurodegenerative diseases.

Methods

We examined preclinical and clinical paradigms that investigated changes in neurodegenerative disease pathology following administration of GLP-1 and GLP-1 RAs. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to September 27th, 2024. Primary studies investigating the aforementioned changes following GLP-1 and GLP-1 RA administration were retrieved for analysis (n = 62).

Results

GLP-1 and GLP-1 RAs (i.e. dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide) improved cognitive and motor function in neurodegenerative diseases in preclinical and clinical paradigms. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in neuroinflammation, oxidative stress, and proliferative pathways.

Discussion

We observed that GLP-1 and GLP-1 RAs modulate molecular and cellular changes known to govern the phenomenology of neurodegenerative diseases. Future research should examine the interaction between signaling molecules, neuronal subpopulations, and cognitive effects affected by GLP-1 and GLP-1 RA administration.

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胰高血糖素样肽-1在淀粉样蛋白、Tau蛋白和α-突触核蛋白上的作用：神经退行性疾病发展的靶点参与和基本原理

简介胰高血糖素样肽-1（GLP-1）和胰高血糖素样肽-1 受体激动剂（GLP-1 RA）与神经退行性疾病的神经保护作用有关。我们对已知的 GLP-1 和 GLP-1 RAs 对神经退行性疾病的认知、细胞和分子变化的影响进行了全面综述。方法我们研究了临床前和临床范例，这些范例调查了服用 GLP-1 和 GLP-1 RAs 后神经退行性疾病病理学的变化。我们通过 OVID（MedLine、Embase、AMED、PsychINFO、JBI EBP Database）、PubMed 和 Web of Science 检索了从数据库建立到 2024 年 9 月 27 日期间的相关文章。结果GLP-1和GLP-1 RAs（即度拉鲁肽、艾塞那肽、利拉鲁肽、利希那肽、赛马鲁肽和替扎帕肽）在临床前和临床范例中改善了神经退行性疾病患者的认知和运动功能。此外，GLP-1 和 GLP-1 RAs 与调节神经炎症、氧化应激和增殖途径的变化有关。未来的研究应探讨信号分子、神经元亚群以及服用 GLP-1 和 GLP-1 RA 所影响的认知效应之间的相互作用。

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

Neuroscience and Biobehavioral Reviews 医学-行为科学

CiteScore

14.20

自引率

3.70%

发文量

466

审稿时长

6 months

期刊介绍： The official journal of the International Behavioral Neuroscience Society publishes original and significant review articles that explore the intersection between neuroscience and the study of psychological processes and behavior. The journal also welcomes articles that primarily focus on psychological processes and behavior, as long as they have relevance to one or more areas of neuroscience.