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帕金森病中P2X7受体发病机制及治疗的新见解。

New insights into pathogenisis and therapies of P2X7R in Parkinson's disease.

作者信息

Wei Shizhuang, Song Xiaoyu, Mou Yakui, Yang Ting, Wang Yao, Wang Hanrui, Ren Chao, Song Xicheng

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.

Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

NPJ Parkinsons Dis. 2025 May 5;11(1):108. doi: 10.1038/s41531-025-00980-7.

DOI:10.1038/s41531-025-00980-7
PMID:40325043
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12053563/
Abstract

Parkinson's disease (PD), a prevalent neurodegenerative disorder, is linked to genetics and environment, but its mechanisms remain unclear. Emerging evidence connects purinergic signaling-particularly ATP-sensitive P2X7 receptor (P2X7R)-to PD. P2X7R expression is elevated in PD patients, and its antagonist BBG mitigates 6-OHDA-induced dopaminergic neuron death. This review discusses P2X7R's structure, neural functions, PD-related mechanisms, and therapeutic potential as a targert.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,与遗传和环境因素有关,但其发病机制仍不清楚。越来越多的证据表明嘌呤能信号传导,特别是三磷酸腺苷敏感的P2X7受体(P2X7R)与帕金森病有关。P2X7R在帕金森病患者中的表达升高,其拮抗剂BBG可减轻6-羟基多巴胺诱导的多巴胺能神经元死亡。本文综述了P2X7R的结构、神经功能、与帕金森病相关的机制以及作为靶点的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/490a91f0964c/41531_2025_980_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/bfe0104533ff/41531_2025_980_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/5c74ea4e66e1/41531_2025_980_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/9f254e336fc8/41531_2025_980_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/490a91f0964c/41531_2025_980_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/bfe0104533ff/41531_2025_980_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/5c74ea4e66e1/41531_2025_980_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/9f254e336fc8/41531_2025_980_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deca/12053563/490a91f0964c/41531_2025_980_Fig4_HTML.jpg

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本文引用的文献

1
Druggable targets for Parkinson's disease: transcriptomics based Mendelian randomization study.帕金森病的可用药靶标:基于转录组学的孟德尔随机化研究。
Sci Rep. 2024 Oct 28;14(1):25763. doi: 10.1038/s41598-024-77401-x.
2
Human P2X7 receptor variants Gly150Arg and Arg276His polymorphisms have differential effects on risk association and cellular functions in pancreatic cancer.人类P2X7受体变体Gly150Arg和Arg276His多态性对胰腺癌的风险关联和细胞功能有不同影响。
Cancer Cell Int. 2024 Apr 25;24(1):148. doi: 10.1186/s12935-024-03339-9.
3
Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases.
P2X7 受体在神经退行性疾病中的作用和治疗靶点。
Front Immunol. 2024 Feb 2;15:1345625. doi: 10.3389/fimmu.2024.1345625. eCollection 2024.
4
A current review on P2X7 receptor antagonist patents in the treatment of neuroinflammatory disorders: a patent review on antagonists.一篇关于 P2X7 受体拮抗剂专利治疗神经炎症性疾病的综述:拮抗剂专利综述。
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):4643-4656. doi: 10.1007/s00210-024-02994-z. Epub 2024 Feb 13.
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The pathogenesis of Parkinson's disease.帕金森病的发病机制。
Lancet. 2024 Jan 20;403(10423):293-304. doi: 10.1016/S0140-6736(23)01478-2.
6
P2X7 Receptor: an Emerging Target in Alzheimer's Disease.P2X7受体:阿尔茨海默病中的一个新兴靶点。
Mol Neurobiol. 2024 May;61(5):2866-2880. doi: 10.1007/s12035-023-03699-9. Epub 2023 Nov 9.
7
Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions.P2RX7 常见遗传变异的特征及其对慢性疼痛疾病的贡献。
J Pain. 2024 Feb;25(2):545-556. doi: 10.1016/j.jpain.2023.09.011. Epub 2023 Sep 22.
8
Characterization of the central nervous system penetrant and selective purine P2X7 receptor antagonist JNJ-54175446 in patients with major depressive disorder.在患有重度抑郁症的患者中,中枢神经系统渗透和选择性嘌呤 P2X7 受体拮抗剂 JNJ-54175446 的特征。
Transl Psychiatry. 2023 Jul 24;13(1):266. doi: 10.1038/s41398-023-02557-5.
9
Ankylosing spondylitis PET imaging and quantifications via P2X7 receptor-targeting radioligand [F]GSK1482160.通过靶向P2X7受体的放射性配体[F]GSK1482160对强直性脊柱炎进行PET成像及定量分析
Eur J Nucl Med Mol Imaging. 2023 Oct;50(12):3589-3601. doi: 10.1007/s00259-023-06342-w. Epub 2023 Jul 19.
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