Purinergic Signalling最新文献

{"title":"Purinergic P2X7 receptor signaling in anxiety: Roles of stress-related neuroinflammatory mechanisms and therapeutic horizons.","authors":"Simranpreet Kaur, Vikash Kumar Giri, Khadga Raj Aran","doi":"10.1007/s11302-026-10134-w","DOIUrl":"10.1007/s11302-026-10134-w","url":null,"abstract":"<p><p>Anxiety is a psychological state marked by constant uneasiness, fear, or stress in response to an actual or perceived danger, resulting in physical changes such as elevated cardiac activity, poor concentration, and restlessness. The excessive stimulation of these responses results in anxiety disorders that disrupt daily activities and even impact familial and social life. The purinergic P2X7 receptor (P2X7R), a ligand-gated ion channel, is predominantly expressed in microglia and serves as a vital detector of cellular stress and injury in the central nervous system (CNS). P2X7R activation requires a high concentration of extracellular adenosine triphosphate (ATP); therefore, it is closely associated with cellular stress. Research has demonstrated that chronic stress inhibits Na⁺/K⁺-ATPase (NKA1) on the cell surface of microglia, thereby increasing the P2X7R expression. The hyperactivity of this receptor contributes to neuroinflammation and, consequently, promotes anxiety-like behaviours. The role of P2X7R in psychostimulant addiction, such as methamphetamine (METH), is complex, but increasing evidence illustrates its activation with neuroinflammation, relapse, and increased dependency. The cumulative stress activates the P2X7R, resulting in amplification of interleukin-17A (IL-17A) levels in the prefrontal cortex (PFC) and amygdala, which intensifies anxiety levels during a psychostimulant withdrawal. Future investigation should concentrate on the development of highly selective P2X7R antagonists and their ability to transverse the blood-brain barrier (BBB), as well as the incorporation of genetic information to enhance personalised therapy methods. This article aims to explore the molecular pathways and neurobehavioral processes of P2X7R in anxiety, highlight therapeutic advances, and outline future directions for translational neuropharmacology.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"21"},"PeriodicalIF":2.5,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In tribute to Francesco Di Virgilio, a great scientist and a wonderful friend.","authors":"Simonetta Falzoni, Anna Lisa Giuliani, Elena Adinolfi, Robson Coutinho-Silva, Peter Illes, Simon C Robson, Yong Tang, Henning Ulrich, Charles Kennedy","doi":"10.1007/s11302-026-10135-9","DOIUrl":"10.1007/s11302-026-10135-9","url":null,"abstract":"<p><p>Francesco Di Virgilio, one of the giants of purinergic signalling, died suddenly on September 22, 2024, which is an immense loss to so many friends and colleagues and especially to his beloved wife, Dorianna. Here, 1 year on, we pay tribute to him and his immense contribution to our field. Francesco graduated in medicine from the University of Padova, Italy, in 1979, with what became a lifelong interest in inflammation. He then held post-doctoral positions at University College London, Padova University, and Columbia University, New York, where he became acquainted with P2X7 receptors. He then returned to Padova as an Associate Professor of Molecular Pathology before moving to the University of Ferrara in 1992, where he set up a world-leading lab that studied the roles and underlying cellular mechanisms of the action of P2X7 receptors in inflammatory pathologies. Francesco published over 370 peer-reviewed articles, which have been cited > 35,000 times, giving him an H-index > 100. In addition, he filed several patents related to purinergic signalling. He also collaborated extensively, both within the University of Ferrara and worldwide, including in universities in the UK, Spain, Germany, the USA, and Brazil. Francesco was a man of great passion and intellect, who possessed scientific vision, intuition, and integrity, and he became the go-to world expert on P2X7 receptors and inflammation. We have lost a giant in the field and a dear friend, but he leaves behind an exceptional body of work, an outstanding legacy, and many friends who will miss him.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"20"},"PeriodicalIF":2.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12900987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-driven purinergic signalling promotes RBFOX1 loss and chemotherapy-induced cardiotoxicity.","authors":"Abdel-Aziz S Shatat","doi":"10.1007/s11302-026-10131-z","DOIUrl":"10.1007/s11302-026-10131-z","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"19"},"PeriodicalIF":2.5,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A_2AR antagonist IDPU facilitates the restoration of mitochondrial dynamics in 6-OHDA-induced primary mid-brain neuronal cells, via regulating p38MAPK/Parkin/DJ-1/DRP1 axis.","authors":"Vaishali Walecha, Jyoti Mishra, Tuithung Sophronea, Namrata Kumari, Pratibha Mehta Luthra","doi":"10.1007/s11302-025-10124-4","DOIUrl":"10.1007/s11302-025-10124-4","url":null,"abstract":"<p><p>Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine receptors (A_2ARs) modulate the striatopallidal non-dopaminergic pathway to alleviate PD symptoms. In the present study, the neuroprotective mechanism of the selective A_2AR antagonist exhibiting a non-purine scaffold, IDPU (K_i = 0.0038 nM), was explored using the primary mid-brain neuronal (PMDN) cells isolated from P₀/P₁ rat pups that differentiated to form dopaminergic neurons, as validated using tyrosine hydroxylase. PMDN cells, when treated with IDPU (0-10 μM) alone, showed insignificant toxicity. However, they exhibited < 60% cell viability when treated with 6-OHDA (150 μM) after 24h. Cell viability improved to > 80%, and dopamine levels were restored in 6-OHDA- (150 μM) induced PMDN cells when 3h post-treated with IDPU (0.7 μM, 1 μM), including the depletion in ROS generation and [Ca²⁺]_i levels observed after 24h. IDPU treatment further impacts the mitochondrial control by attenuating both mitochondrial SOD production and its membrane potential loss in PD-like conditions. To investigate the mechanism of A_2AR intervention on governing the mitochondrial-associated signalling cascades, the proteins were isolated from 6-OHDA (150 μM) induced PMDN cells 3h post-treated with IDPU (0.7 μM, 1 μM) and ZM241385 (1 μM) for western blot analysis. Our results exhibited that the phosphorylation of both DRP1 (Ser616) (78 kDa) and p38MAPK (Tyr182) (41 kDa) proteins was enhanced when exposed to 6-OHDA; however, the protein levels reduced post-treatment with both A_2AR antagonists. In contrast, 6-OHDA toxicity alleviated the levels of both Parkin (58 kDa) and DJ-1(23 kDa), while exposure to A_2AR antagonists (IDPU and ZM241385) improved their protein levels. This suggests the possible involvement of A_2AR blockade in regulating mitochondrial dynamics, thus promoting survival. These findings present the first evidence that IDPU demonstrates neuroprotection in PDlike conditions via the p38MAPK/DRP1/Parkin signalling, offering a potential therapeutic mechanism for targeting mitochondrial dynamics through A_2AR antagonism.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"18"},"PeriodicalIF":2.5,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X4 receptors on myeloid cells mediate tissue injury in a model of trauma and hemorrhagic shock in male mice.","authors":"Taha Kelestemur, Zoltán H Németh, Pal Pacher, Burhan Yokus, H Thomas Lee, Mihwa Kim, Mehmet S Aydin, Ugur Akcan, György Haskó","doi":"10.1007/s11302-026-10132-y","DOIUrl":"10.1007/s11302-026-10132-y","url":null,"abstract":"<p><p>Trauma and hemorrhagic shock (T/HS) trigger systemic inflammation and multiorgan injury, yet the molecular mediators of this response remain incompletely defined. Purinergic receptors, including P2X4 and P2X7, are key regulators of innate immune signaling and may contribute to post-trauma organ dysfunction. Here, we assessed the roles of P2X4 and P2X7 in T/HS-induced injury across multiple organs using genetic and pharmacologic approaches in murine models. Global P2X4 knockout (KO) mice exhibited significantly reduced injury in the lung as reflected by improved histopathology, decreased myeloperoxidase activity, and preserved tissue architecture. Additionally, P2X4 KO reduced liver and kidney injury, as indicated by plasma liver enzymes and blood urea nitrogen levels. Myeloid-specific P2X4 deficiency recapitulated these protective effects, suggesting a central role for myeloid cell-mediated P2X4 signaling in multiorgan injury. Bulk RNA sequencing of lung tissue from P2X4 KO mice revealed altered expression of immune response genes, including downregulation of P2X7. Pharmacological inhibition of P2X7 reduced injury in the lung, liver, and kidney. Both P2X4 and P2X7 expressions were downregulated in affected organs following T/HS. These findings identify P2X4, particularly in myeloid cells, as a key driver of multiorgan injury following T/HS, and support further investigation of P2 receptor modulation as a therapeutic strategy in trauma-induced organ injury.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"16"},"PeriodicalIF":2.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12868421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine: potential target as rapid-acting antidepressants.","authors":"Jia-Jia Li, Yong Tang, Peter Illes","doi":"10.1007/s11302-026-10133-x","DOIUrl":"10.1007/s11302-026-10133-x","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"17"},"PeriodicalIF":2.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12873011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brilliant blue G enhances cardiac function and suppresses ventricular arrhythmias by attenuating inflammation and fibrosis after post-myocardial infarction in rats.","authors":"Zefei Jiang, Xuan Li, Masaomi Miura, Xiaoxiang Sun, Xiaohua Peng, Qiulian Lei, Rauza Sukma Rita, Yue Feng, Enxu Li, Xin Cao","doi":"10.1007/s11302-025-10116-4","DOIUrl":"10.1007/s11302-025-10116-4","url":null,"abstract":"<p><p>Myocardial infarction (MI) is a leading cause of heart failure and ventricular arrhythmias, driven by excessive inflammation and adverse cardiac remodeling. The purinergic P2X7 receptor (P2X7R) plays a critical role in acute MI, however, the long-term effect of P2X7R on chronic MI and arrhythmia remains unknown. This study investigated the effects of long-term modulation of P2X7R on inflammation, fibrosis, and arrhythmias in a rat model of MI. Male Sprague-Dawley rats underwent left anterior descending coronary artery ligation and were assigned to sham, MI, MI + Brilliant Blue G (BBG, P2X7R antagonist), or MI + BzATP (P2X7R agonist) groups for 28 days. BBG treatment significantly reduced ventricular tachycardia induction rates, shortened QT, QTc, and Tpeak-Tend intervals, and improved cardiac function, as evidenced by increased ejection fraction, fractional shortening, and cardiac output. Histological analyses revealed reduced inflammatory cell infiltration, necrosis, and collagen deposition in the MI + BBG group compared to MI groups. ELISA confirmed that BBG lowered pro-inflammatory cytokines TNF-α, IL-1β and TGF-β1 levels. P2X7 mRNA expression was attenuated by BBG, but not significantly altered. These findings demonstrate that BBG mitigates post-MI inflammation, fibrosis, and arrhythmias while enhancing cardiac function.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"15"},"PeriodicalIF":2.5,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of the P2X1 receptor remains in the type II spiral ganglion neurons in the mature rat cochlea.","authors":"Prakansha N Kumar, Srdjan M Vlajkovic, Peter R Thorne, Haruna Suzuki-Kerr","doi":"10.1007/s11302-026-10129-7","DOIUrl":"10.1007/s11302-026-10129-7","url":null,"abstract":"<p><p>Our sense of hearing commences in the cochlea, the peripheral sensory organ for hearing. Spiral ganglion neurons (SGN) in the cochlea are primary auditory neurons responsible for auditory neurotransmission. There are two classes of SGNs: type I SGNs, which make up 90-95% of the SGN population, and type II SGNs, which make up the remainder. Previous studies have shown that SGNs express a combination of purinergic (P2X, P2Y and adenosine) receptors at the mRNA and protein levels. In this study, we have focused on the P2X1 receptor to characterise its expression pattern in the Wistar rat cochlea at postnatal day 8 and in adult (6-8-week-old) rats of both genders using immunohistochemistry. Our results show differential expression of P2X1 receptors in 9.4-14.2% of SGNs in the adult cochlea, and 14.2-23.3% in the cochlea of P8 pups. In most of these neurons, P2X1 receptors were co-expressed with peripherin-1, an established type II SGN marker. These results suggest a potential role for the P2X1 receptor as a modulator of auditory neurotransmission in type II spiral ganglion neurons.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"14"},"PeriodicalIF":2.5,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The purinergic signaling interfaces in breast cancer angiogenesis.","authors":"Fernanda Cardoso da Silva, Jeferson Stabile, Cristina Ribas Fürstenau, Thaise Gonçalves Araújo","doi":"10.1007/s11302-025-10119-1","DOIUrl":"10.1007/s11302-025-10119-1","url":null,"abstract":"<p><p>Cancer is a group of diseases characterized by disordered cell proliferation and loss of tissue architecture. Breast cancer (BC) is the most common and lethal cancer among women, standing out for its molecular, histological and pathological heterogeneity. The BC tumor microenvironment (TME) is a complex ecosystem comprising transformed cells and a multitude of non-tumor cells, embedded in an altered extracellular matrix. Endothelial cells are present, driving angiogenesis, a relevant hallmark that ensures nutrition and oxygenation through the formation of new blood vessels. During this process, a complex network of molecules is released by tumor and endothelial cells, such as Vascular Endothelial Growth Factor (VEGF), that, in turn, induce cancer progression, diffusion, and metastasis. Purinergic signaling also regulates the functioning of endothelial cells involving the action of purines (ATP, ADP, UTP, UDP and adenosine) as signaling in purinergic receptors, with their concentration modulated by enzymes known as ectonucleotidases. This review aims to explore the contribution of purinergic signaling to BC angiogenesis, highlighting potential therapeutic targets currently under scientific focus. In general, the TME presents overexpression of ATP and adenosine, which stimulate endothelial cells through purinergic receptors. This stimulus promotes the formation of new vessels, mainly via the release of VEGF. Thus, purinergic signaling emerges as a central mechanism in BC angiogenesis, with potential to be explored in the development of antitumor therapies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"13"},"PeriodicalIF":2.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X4 receptors as the dynamic regulators of auditory sensory cell activity: a potential new mechanism for protecting hearing?","authors":"Alizée Fisher-Ridoux, Haruna Suzuki-Kerr","doi":"10.1007/s11302-026-10130-0","DOIUrl":"10.1007/s11302-026-10130-0","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":"22 1","pages":"12"},"PeriodicalIF":2.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}