The P2X7 receptor in depression: Novel insights and therapeutic implications
Major depressive disorder (MDD) is a heterogeneous mental disorder involving multiple pathogenic mechanisms. Current first-line antidepressant medications suffer from slow onset of action, limited effectiveness, and high side effects, necessitating the search for new therapeutic targets. Targeting c...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612500227X |
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| author | Yue-ting Zhong Chao Pi Ying Zuo Yan Wei Wen Li Yong-qiang Jiang Lei Tao Wen-wu Zheng Jun Jiang Yan Yang Shi-feng Chu Bin-yan Liu Ke-zhi Liu Yu-meng Wei Ling Zhao |
| author_facet | Yue-ting Zhong Chao Pi Ying Zuo Yan Wei Wen Li Yong-qiang Jiang Lei Tao Wen-wu Zheng Jun Jiang Yan Yang Shi-feng Chu Bin-yan Liu Ke-zhi Liu Yu-meng Wei Ling Zhao |
| author_sort | Yue-ting Zhong |
| collection | DOAJ |
| description | Major depressive disorder (MDD) is a heterogeneous mental disorder involving multiple pathogenic mechanisms. Current first-line antidepressant medications suffer from slow onset of action, limited effectiveness, and high side effects, necessitating the search for new therapeutic targets. Targeting cytokines or receptors is increasingly recognized in innovative depression treatment protocols. The P2X7 receptor (P2X7R) plays a key role in central nervous system signaling and is considered a potential therapeutic target for depression. Recent studies have focused on the fact that P2X7R modulates inflammatory and immune responses, which may contribute to the development of depression. However, the full extent of P2X7R's involvement in depression remains unclear. This review provides a comprehensive overview of the discovery, structure, and properties of P2X7R. We delve into the role of P2X7R in the pathogenesis of depression, focusing on neuroinflammation, oxidative stress, mitochondrial dysfunction, and reduced synaptic plasticity. Additionally, we discuss the clinical applications of P2X7R antagonists. By highlighting the significant role and therapeutic potential of the P2X7 receptor as a pharmacological target for depression, this review aims to provide new research perspectives and theoretical basis for the development of antidepressant drugs. |
| format | Article |
| id | doaj-art-123e9f29ab5d41a28f9fcd25fa26a590 |
| institution | DOAJ |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-123e9f29ab5d41a28f9fcd25fa26a5902025-08-20T02:45:42ZengElsevierNeurobiology of Disease1095-953X2025-09-0121310701110.1016/j.nbd.2025.107011The P2X7 receptor in depression: Novel insights and therapeutic implicationsYue-ting Zhong0Chao Pi1Ying Zuo2Yan Wei3Wen Li4Yong-qiang Jiang5Lei Tao6Wen-wu Zheng7Jun Jiang8Yan Yang9Shi-feng Chu10Bin-yan Liu11Ke-zhi Liu12Yu-meng Wei13Ling Zhao14Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, PR China; Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR China; Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, PR China; Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR ChinaDepartment of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR ChinaLaboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, 646000, PR ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, PR China; Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, PR China; Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, PR China; Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, PR ChinaDepartment of Thyroid Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR ChinaLaboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, 646000, PR ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, PR ChinaDepartment of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Correspondence to: Kezhi Liu, Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan 646000, PR China.Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR China; Correspondence to: Yumeng Wei, Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, No. 1, Section 1, Xianglin Road, Longmatan District, Luzhou, Sichuan 646000, PR China.Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Central Nervous System Product Research and Development Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, PR China; Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, PR China; Correspondence to: Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University; No.182, Chunhui Road, Longmatan District, Luzhou, Sichuan 646000, China.Major depressive disorder (MDD) is a heterogeneous mental disorder involving multiple pathogenic mechanisms. Current first-line antidepressant medications suffer from slow onset of action, limited effectiveness, and high side effects, necessitating the search for new therapeutic targets. Targeting cytokines or receptors is increasingly recognized in innovative depression treatment protocols. The P2X7 receptor (P2X7R) plays a key role in central nervous system signaling and is considered a potential therapeutic target for depression. Recent studies have focused on the fact that P2X7R modulates inflammatory and immune responses, which may contribute to the development of depression. However, the full extent of P2X7R's involvement in depression remains unclear. This review provides a comprehensive overview of the discovery, structure, and properties of P2X7R. We delve into the role of P2X7R in the pathogenesis of depression, focusing on neuroinflammation, oxidative stress, mitochondrial dysfunction, and reduced synaptic plasticity. Additionally, we discuss the clinical applications of P2X7R antagonists. By highlighting the significant role and therapeutic potential of the P2X7 receptor as a pharmacological target for depression, this review aims to provide new research perspectives and theoretical basis for the development of antidepressant drugs.http://www.sciencedirect.com/science/article/pii/S096999612500227XDepressionP2X7 receptorNeuroinflammationOxidative stressMitochondrial dysfunctionSynaptic plasticity |
| spellingShingle | Yue-ting Zhong Chao Pi Ying Zuo Yan Wei Wen Li Yong-qiang Jiang Lei Tao Wen-wu Zheng Jun Jiang Yan Yang Shi-feng Chu Bin-yan Liu Ke-zhi Liu Yu-meng Wei Ling Zhao The P2X7 receptor in depression: Novel insights and therapeutic implications Neurobiology of Disease Depression P2X7 receptor Neuroinflammation Oxidative stress Mitochondrial dysfunction Synaptic plasticity |
| title | The P2X7 receptor in depression: Novel insights and therapeutic implications |
| title_full | The P2X7 receptor in depression: Novel insights and therapeutic implications |
| title_fullStr | The P2X7 receptor in depression: Novel insights and therapeutic implications |
| title_full_unstemmed | The P2X7 receptor in depression: Novel insights and therapeutic implications |
| title_short | The P2X7 receptor in depression: Novel insights and therapeutic implications |
| title_sort | p2x7 receptor in depression novel insights and therapeutic implications |
| topic | Depression P2X7 receptor Neuroinflammation Oxidative stress Mitochondrial dysfunction Synaptic plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S096999612500227X |
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