GLP-1受体激动剂： 一种帕金森病的新兴治疗策略

doi:10.19586/j.2095-2341.2025.0021

生物技术进展 ›› 2025, Vol. 15 ›› Issue (3): 404-410.DOI: 10.19586/j.2095-2341.2025.0021

GLP-1受体激动剂：一种帕金森病的新兴治疗策略

刘艳花(), 郭蕊, 李岩异, 陈金利()

华北制药金坦生物技术股份有限公司，石家庄 050035

收稿日期:2025-02-21 接受日期:2025-04-01 出版日期:2025-05-25 发布日期:2025-07-01
通讯作者: 陈金利
作者简介:刘艳花 E-mail: 395375685@qq.com；

GLP-1 Receptor Agonists: Emerging Therapeutic Strategy for Parkinson‍'‍s Disease

Yanhua LIU(), Rui GUO, Yanyi LI, Jinli CHEN()

North China Pharmaceutical Genetech Biotechnology Co. ，Ltd. ，Shijiazhuang 050035，China

Received:2025-02-21 Accepted:2025-04-01 Online:2025-05-25 Published:2025-07-01
Contact: Jinli CHEN

摘要/Abstract

摘要：

帕金森病(Parkinson’s disease，PD)是最常见的神经退行性疾病之一。最新研究数据揭示了神经退行性疾病与2型糖尿病(type 2 diabetes mellitus，T2DM)可能存在相似的药理机制。胰高血糖素样肽-1受体(glucagon-like peptide-1 receptor，GLP-1R)激动剂作为治疗T2DM用药，目前也被尝试用于治疗PD。综述总结了T2DM与PD之间可能的共同致病途径，探讨了GLP-1受体激动剂作为PD治疗靶点的潜在作用机制，以期为开发更有效的PD治疗方案提供理论支持。

关键词: 帕金森病, 2型糖尿病, GLP-1R激动剂, 神经退行性疾病

Abstract:

Parkinson's disease （PD） is one of the most common neurodegenerative diseases. The latest research data reveal that neurodegenerative diseases and type 2 diabetes （T2DM） may have similar pharmacological mechanisms. Glucagon like peptide-1 receptor （GLP-1R） agonists are widely known for their successful application in the treatment of T2DM and are currently studied as a novel PD therapeutic drug. This review summarized the possible co-pathogenic pathways between T2DM and PD， and discussed the potential mechanism of action of GLP-1R agonists as targets for PD treatment， in order to provide theoretical support for the development of more effective PD treatment plans.

Key words: Parkinson's disease, type 2 diabetes, GLP-1R agonist, neurodegenerative diseases

中图分类号:

Q189

刘艳花, 郭蕊, 李岩异, 陈金利. GLP-1受体激动剂：一种帕金森病的新兴治疗策略[J]. 生物技术进展, 2025, 15(3): 404-410.

Yanhua LIU, Rui GUO, Yanyi LI, Jinli CHEN. GLP-1 Receptor Agonists: Emerging Therapeutic Strategy for Parkinson‍'‍s Disease[J]. Current Biotechnology, 2025, 15(3): 404-410.

参考文献 25

1	FAHN S. Description of Parkinson's disease as a clinical syndrome[J]. Ann. NY Acad. Sci., 2003, 991: 1-14.
2	KALINDERI K, PAPALIAGKAS V, FIDANI L. The genetic landscape of sleep disorders in Parkinson's disease[J/OL]. Diagnostics, 2024, 14(1): 106[2025-04-21]. .
3	KALINDERI K, PAPALIAGKAS V, FIDANI L. Current genetic data on depression and anxiety in Parkinson's disease patients[J/OL]. Parkinsonism Relat. Disord., 2024, 118: 105922[2025-04-21]. .
4	KALINDERI K, PAPALIAGKAS V, FIDANI L. Pharmacogenetics and levodopa induced motor complications[J]. Int. J. Neurosci., 2019, 129(4): 384-392.
5	MICHAILIDIS M, MORAITOU D, TATA D A, et al.. Alzheimer's disease as type 3 diabetes: common pathophysiological mechanisms between Alzheimer's disease and type 2 diabetes[J/OL]. Int. J. Mol. Sci., 2022, 23(5): 2687[2025-04-21]. .
6	BRAUER R, WEI L, MA T, et al.. Diabetes medications and risk of Parkinson's disease: a cohort study of patients with diabetes[J]. Brain, 2020, 143(10): 3067-3076.
7	MALHOTRA K, KATSANOS A H, LAMBADIARI V, et al.. GLP-1 receptor agonists in diabetes for stroke prevention: a systematic review and meta-analysis[J]. J. Neurol., 2020, 267(7): 2117-2122.
8	PERRY T, HAUGHEY N J, MATTSON M P, et al.. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4[J]. J. Pharmacol. Exp. Ther., 2002, 302(3): 881-888.
9	STUMVOLL M, GOLDSTEIN B J, VAN HAEFTEN T W. Type 2 diabetes: principles of pathogenesis and therapy[J]. Lancet, 2005, 365(9467): 1333-1346.
10	KOMICI K, FEMMINELLA G D, BENCIVENGA L, et al.. Diabetes mellitus and Parkinson's disease: a systematic review and meta-analyses[J]. J. Parkinsons Dis., 2021, 11(4): 1585-1596.
11	YANG Y W, FHSIEH T, LI C I, et al.. Increased risk of Parkinson disease with diabetes mellitus in a population-based study[J/OL]. Medicine, 2017, 96(3): e5921[2025-04-21]. .
12	FERRARI F, MORETTI A, VILLA R F. Incretin-based drugs as potential therapy for neurodegenerative diseases: current status and perspectives[J/OL]. Pharmacol. Ther., 2022, 239: 108277[2025-04-21]. .
13	HONG C T, CHEN K Y, WANG W, et al.. Insulin resistance promotes Parkinson's disease through aberrant expression of α‍-synuclein, mitochondrial dysfunction, and deregulation of the polo-like kinase 2 signaling[J/OL]. Cells, 2020, 9(3): 740[2025-04-21]. .
14	WANG L, ZHAI Y Q, XU L L, et al.. Metabolic inflammation exacerbates dopaminergic neuronal degeneration in response to acute MPTP challenge in type 2 diabetes mice[J]. Exp. Neurol., 2014, 251: 22-29.
15	GARCIA-GARCIA D, CLAVERO P, GASCA SALAS C, et al.. Posterior parietooccipital hypometabolism may differentiate mild cognitive impairment from dementia in Parkinson's disease[J]. Eur. J. Nucl. Med. Mol. Imaging, 2012, 39(11): 1767-1777.
16	BARBIERO J K, SANTIAGO R M, PERSIKE D S, et al.. Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of Parkinsonism induced by intranigral 1-methyl-4-phenyl-1, 2, 3, 6-tetrahyropyridine[J]. Behav. Brain Res., 2014, 274: 390-399.
17	IRAVANPOUR F, DARGAHI L, REZAEI M, et al.. Intranasal insulin improves mitochondrial function and attenuates motor deficits in a rat 6-OHDA model of Parkinson's disease [J]. CNS Neurosci. Ther., 2021, 27(3): 308-319.
18	NOVAK P, PIMENTEL MALDONADO D A, NOVAK V. Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson's disease and multiple system atrophy: a double-blinded placebo-controlled pilot study[J/OL]. PLoS ONE, 2019, 14(4): e0214364[2025-04-21]. .
19	HÖLSCHER C. Brain insulin resistance: role in neurodegenerative disease and potential for targeting[J]. Expert Opin. Investig. Drugs, 2020, 29(4): 333-348.
20	DRUCKER D J. Mechanisms of action and therapeutic application of glucagon-like peptide-1[J]. Cell Metab., 2018, 27(4): 740-756.
21	KOPP K O, GLOTFELTY E J, LI Y, et al.. Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: implications for neurodegenerative disease treatment[J/OL]. Pharmacol. Res., 2022, 186: 106550[2025-04-21]. .
22	DRUCKER D J, NAUCK M A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes[J]. Lancet, 2006, 368(9548): 1696-1705.
23	LIU D X, ZHAO C S, WEI X N, et al.. Semaglutide protects against 6-OHDA toxicity by enhancing autophagy and inhibiting oxidative stress[J/OL]. Parkinsons Dis., 2022, 2022: 6813017[2025-04-21]. .
24	ZHOU Z D, YI L X, WANG D Q, et al.. Role of dopamine in the pathophysiology of Parkinson's disease[J/OL]. Transl. Neurodegener., 2023, 12(1): 44[2025-04-21]. .
25	KALINDERI K, GOULA V, SAPOUNTZI E, et al.. Syndromic and monogenic obesity: new opportunities due to genetic-based pharmacological treatment[J/OL]. Children, 2024, 11(2): 153[2025-04-21]. .

[1]	邱思元, 闫立地, 赵文婧, 赵金玉, 段育阳, 王桐. 程序性坏死发生机制在帕金森病中作用的研究进展[J]. 生物技术进展, 2023, 13(3): 406-411.
[2]	赵鹏翔, 谢飞, 刘梦昱, ADZAVON Yao Mawulikplimi, 马雪梅. 氢气生物医学研究进展[J]. 生物技术进展, 2021, 11(4): 503-517.
[3]	廖敏,杨洛,王珍,郝亚荣. 抗糖尿病药物治疗阿尔茨海默病的研究进展[J]. 生物技术进展, 2021, 11(3): 311-315.
[4]	张凯艺,谢宁,叶华琼,杨述林. 葡萄糖转运蛋白在血糖稳态调节中的功能[J]. 生物技术进展, 2019, 9(1): 21-27.
[5]	陈枕枕,牛昱宇. 诱导多能干细胞在帕金森病治疗中的应用进展[J]. 生物技术进展, 2018, 8(6): 517-521.
[6]	杨玉洁,李楠. 硒蛋白与神经退行性疾病[J]. 生物技术进展, 2017, 7(5): 511-517.

GLP-1受体激动剂：一种帕金森病的新兴治疗策略

GLP-1 Receptor Agonists: Emerging Therapeutic Strategy for Parkinson‍'‍s Disease

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 25

相关文章 6

编辑推荐

Metrics

本文评价

GLP-1受体激动剂： 一种帕金森病的新兴治疗策略

GLP-1 Receptor Agonists: Emerging Therapeutic Strategy for Parkinson‍'‍s Disease

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 25

相关文章 6

编辑推荐

Metrics

本文评价

GLP-1受体激动剂：一种帕金森病的新兴治疗策略