胰高血糖素样肽-1 （GLP-1）受体激动剂是否具有中枢神经系统（CNS）渗透性？

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-04-02 DOI:10.1007/s40120-025-00724-y

Juliana West, Maggie Li, Sabrina Wong, Gia Han Le, Kayla M Teopiz, Kyle Valentino, Christine E Dri, Roger S McIntyre

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引用次数: 0

摘要

胰高血糖素样肽-1 （Glucagon-like peptide-1, GLP-1）是一种调节葡萄糖代谢和胰岛素分泌的肠促胰岛素激素。最近的转化和临床研究已经评估了GLP-1受体激动剂（GLP-1 RAs）的作用，这是一类模仿中枢神经系统（CNS）中天然GLP-1作用的药物。除了GLP-1治疗糖尿病和肥胖症的疗效外，初步证据表明，GLP-1对某些神经退行性疾病（如帕金森病、阿尔茨海默病）具有神经保护、治疗和疾病修饰作用。在可用的GLP-1 RAs中，相对较少被证明是中枢神经系统渗透的。本文综合现有文献报道GLP-1 RAs在中枢神经系统渗透的脑成像研究。在可用的情况下，研究报告了GLP-1 RAs在中枢神经系统中的生物利用度。方法：综合检索PubMed、Ovid和Web of Science自建库至2024年7月的数据库。纳入标准为无日期限制的英文出版物、18-80岁受试者的临床前和临床研究，以及关注GLP-1 RAs的研究，包括：“Semaglutide”、“Ozempic”、“Rybelsus”、“Wegovy”、“Dulaglutide”、“Trulicity”、“Exenatide”、“Byetta”、“Bydureon”、“Liraglutide”、“Lixisenatide”、“tizepatide”、“Mounjaro”、“Zepbound”、“Bydureon BCise”、“Adlyxin”、“Victoza”或“Saxenda”。结果：我们确定了14项研究纳入该综合。临床前研究表明，部分GLP-1 RAs可穿过血脑屏障（BBB）（即利拉鲁肽、西马鲁肽和艾塞那肽）。重复的证据表明，GLP-1 RAs对中枢神经系统的渗透可以通过报道的GLP-1 RAs对人类参与者大脑连接的影响来代替。结论：临床前研究表明，部分GLP-1 RAs具有中枢神经系统渗透作用；GLP-1 RAs是否可重复地参与精神病理维度（如一般认知功能）假设的神经靶点仍未完全确定。

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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Are Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Central Nervous System (CNS) Penetrant: A Narrative Review.

Introduction: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that modulates glucose metabolism and insulin secretion. Recent translational and clinical research has evaluated the effects of GLP-1 receptor agonists (GLP-1 RAs), a class of drugs that mimic the action of native GLP-1 in the central nervous system (CNS). In addition to the efficacy of GLP-1 for the treatment of diabetes mellitus and obesity, preliminary evidence indicates GLP-1s have neuroprotective, therapeutic, and disease modification effects for select neurodegenerative disorders (e.g. Parkinson's disease, Alzheimer's disease). Among the available GLP-1 RAs, relatively few have been shown to be CNS penetrant. This article synthesizes extant literature reporting on CNS penetrants of GLP-1 RAs as proxied by brain imaging studies. Where available, studies that reported on the bioavailability of GLP-1 RAs in the CNS were identified.

Methods: A comprehensive search of PubMed, Ovid, and Web of Science from database inception to July 2024 was conducted. Inclusion criteria were English language publications with no date restrictions, preclinical and clinical studies with participants aged 18-80 and studies which focused on GLP-1 RAs including: "Semaglutide" or "Ozempic" or "Rybelsus" or "Wegovy" or "Dulaglutide" or "Trulicity" or "Exenatide" or "Byetta" or "Bydureon" or "Liraglutide" or "Lixisenatide" or "Tirzepatide" or "Mounjaro" or "Zepbound" or "Bydureon BCise" or "Adlyxin" or "Victoza" or "Saxenda".

Results: We identified 14 studies that were included in this synthesis. Preclinical studies suggest that select GLP-1 RAs cross the blood-brain barrier (BBB) (i.e. liraglutide, semaglutide, and exenatide). Replicated evidence suggests that CNS penetration of GLP-1 RAs can be proxied by reported effects of GLP-1 RAs on brain connectivity in human participants.

Conclusion: Preclinical studies indicate that select GLP-1 RAs are CNS penetrant; whether GLP-1 RAs reproducibly engage neural targets hypothesized to subserve dimensions of psychopathology (e.g., general cognitive functions) remains incompletely characterized.

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

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