P2X7 receptor: a potential target for treating comorbid anxiety and depression

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-04-20 DOI:10.1007/s11302-024-10007-0
Jun Liu, Ting-Ting Liu, Lan Mou, Yuwen Zhang, Xiang Chen, Qi Wang, Bin-Lu Deng, Jie Liu
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Abstract

In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5’-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.

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P2X7 受体:治疗合并焦虑症和抑郁症的潜在靶点
在临床实践中,抑郁和焦虑经常同时存在,而且它们都与躯体疾病并发。P2X7R 是一种腺苷-5'-三磷酸(ATP)门控的非选择性阳离子通道,在免疫相关细胞中广泛表达。在压力、慢性疼痛和合并慢性身体疾病的情况下,神经胶质细胞中的 P2X7R 激活会导致神经炎症。这可能会导致焦虑和抑郁相关的情绪紊乱。以往的研究表明,P2X7 受体(P2X7R)在焦虑症和抑郁症的发病机制中发挥着重要作用。因此,P2X7R 可能在焦虑症和抑郁症的并发症中发挥作用。正电子发射断层扫描可通过监测 P2X7R 的功能和表达相关变化来评估神经炎症的程度和位置,从而有助于焦虑症和抑郁症患者的临床诊断和指导治疗。此外,P2X7R 基因的单核苷酸多态性(SNPs)与不同类型精神疾病的易感性有关。因此,评估 P2X7R 基因的 SNPs 可以实现情绪障碍的个性化诊断和治疗。如果将 P2X7R 设为治疗靶点,选择性 P2X7R 拮抗剂可能会调节 P2X7R 的功能,从而改变细胞内外 ATP 的平衡。这可能对治疗焦虑症和抑郁症以及疼痛有治疗意义。根据体外和体内研究,P2X7R 在焦虑和抑郁中发挥着重要作用。在这篇综述中,我们探讨了 P2X7R 作为合并焦虑症和抑郁症治疗靶点的潜力,并讨论了该受体的潜在诊断和治疗价值。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
期刊最新文献
Correction to: Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist. Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. Purinergic regulation of pulmonary vascular tone. Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility. Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia.
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