Purinergic Signalling最新文献_第3页

P2 purinergic receptor expression and function in tumor-related immune cells. 肿瘤相关免疫细胞中 P2 嘌呤能受体的表达和功能。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-10 DOI: 10.1007/s11302-024-10054-7

Vahinipriya Manoharan, Oluwafemi O Adegbayi, Janielle P Maynard

{"title":"P2 purinergic receptor expression and function in tumor-related immune cells.","authors":"Vahinipriya Manoharan, Oluwafemi O Adegbayi, Janielle P Maynard","doi":"10.1007/s11302-024-10054-7","DOIUrl":"https://doi.org/10.1007/s11302-024-10054-7","url":null,"abstract":"P2 purinergic receptor expression is dysregulated in multiple cancer subtypes and is associated with worse outcomes. Studies identify roles for P2 purinergic receptors in tumor cells that drive disease aggressiveness. There is also sufficient evidence that P2 purinergic receptor expression within the tumor microenvironment (TME) is critical for disease initiation and progression. Immune cells constitute a significant component of the TME and display both tumorigenic and anti-tumorigenic potential. Studies pre-dating the investigation of P2 purinergic receptors in cancer identify P2 receptor expression on multiple immune cells including macrophages, neutrophils, T-cells, and dendritic cells; all of which are implicated in tumor initiation, tumor promotion, or response to treatment. Herein, we discuss P2 purinergic receptor expression and function in tumor-related immune cells. We provide a rationale for further investigations of P2 purinergic receptors within the TME to better define the mechanistic pathways of inflammation-mediate tumorigenesis and explore P2 purinergic receptors as potential targets for novel immunotherapeutic approaches.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis. 巴西利什曼原虫重组核苷三磷酸二磷酸水解酶2 (LbNTPDase2)的异源表达及生化特性研究。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2023-11-24 DOI: 10.1007/s11302-023-09980-9

Nancy da Rocha Torres Pavione, João Victor Badaró de Moraes, Isadora Cunha Ribeiro, Raissa Barbosa de Castro, Walmir da Silva, Anna Cláudia Alves de Souza, Victor Hugo Ferraz da Silva, Raphael de Souza Vasconcellos, Gustavo da Costa Bressan, Juliana Lopes Rangel Fietto

{"title":"Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.","authors":"Nancy da Rocha Torres Pavione, João Victor Badaró de Moraes, Isadora Cunha Ribeiro, Raissa Barbosa de Castro, Walmir da Silva, Anna Cláudia Alves de Souza, Victor Hugo Ferraz da Silva, Raphael de Souza Vasconcellos, Gustavo da Costa Bressan, Juliana Lopes Rangel Fietto","doi":"10.1007/s11302-023-09980-9","DOIUrl":"10.1007/s11302-023-09980-9","url":null,"abstract":"Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"509-520"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299840","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}

引用次数: 0

Role of CD73 and the purinergic signaling pathway in the pathogenesis of fusion-negative rhabdomyosarcoma. CD73和嘌呤能信号通路在融合阴性横纹肌肉瘤发病机制中的作用

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-05-03 DOI: 10.1007/s11302-024-10013-2

Amelia Fascì, Silvia Deaglio

引用次数: 0

Promoting glymphatic flow: A non-invasive strategy using 40 Hz light flickering. 促进淋巴流动：使用 40 Hz 灯光闪烁的非侵入性策略。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 DOI: 10.1007/s11302-024-10052-9

Jianchen Fan, Zhihua Gao

{"title":"Promoting glymphatic flow: A non-invasive strategy using 40 Hz light flickering.","authors":"Jianchen Fan, Zhihua Gao","doi":"10.1007/s11302-024-10052-9","DOIUrl":"https://doi.org/10.1007/s11302-024-10052-9","url":null,"abstract":"The glymphatic system is critical for brain homeostasis by eliminating metabolic waste, whose disturbance contributes to the accumulation of pathogenic proteins in neurodegenerative diseases. Promoting glymphatic clearance is a potential and attractive strategy for several brain disorders, including neurodegenerative diseases. Previous studies have uncovered that 40 Hz flickering augmented glymphatic flow and facilitated sleep (Zhou et al. in Cell Res 34:214-231, 2024) since sleep drives waste clearance via glymphatic flow (Xie et al. in Science 342:373-377, 2013). However, it remains unclear whether 40 Hz light flickering directly increased glymphatic flow or indirectly by promoting sleep. A recent article published in Cell Discovery by Chen et al. (Sun et al. in Cell Discov 10:81, 2024) revealed that 40 Hz light flickering facilitated glymphatic flow, by promoting the polarization of astrocytic aquaporin-4 (AQP4) and vasomotion through upregulated adenosine-A2A receptor (A2AR) signaling, independent of sleep. These findings suggest that 40 Hz light flickering may be used as a non-invasive approach to control the function of the glymphatic-lymphatic system, to help remove metabolic waste in the brain, thereby presenting a potential strategy for neurodegenerative disease treatment.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Purines and purinergic receptors in primary tumors of the central nervous system. 中枢神经系统原发性肿瘤中的嘌呤和嘌呤能受体。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 DOI: 10.1007/s11302-024-10053-8

Adinei Abadio Soares, Helamã Moraes Dos Santos, Keyllor Nunes Domann, Natália Pratis Rocha Alves, Bernardo Ribeiro Böhm, Carolina Maliska Haack, Kailane Paula Pretto, Emily Sanini Guimarães, Guilherme Francisquini Rocha, Igor Rodrigues de Paula, Lucas Efraim de Alcântara Guimarães, Harlan Cleyton de Ávila Pessoa, Robison David Rodrigues, Angela Makeli Kososki Dalagnol, Marcelo Lemos Vieira da Cunha, Débora Tavares de Resende E Silva

{"title":"Purines and purinergic receptors in primary tumors of the central nervous system.","authors":"Adinei Abadio Soares, Helamã Moraes Dos Santos, Keyllor Nunes Domann, Natália Pratis Rocha Alves, Bernardo Ribeiro Böhm, Carolina Maliska Haack, Kailane Paula Pretto, Emily Sanini Guimarães, Guilherme Francisquini Rocha, Igor Rodrigues de Paula, Lucas Efraim de Alcântara Guimarães, Harlan Cleyton de Ávila Pessoa, Robison David Rodrigues, Angela Makeli Kososki Dalagnol, Marcelo Lemos Vieira da Cunha, Débora Tavares de Resende E Silva","doi":"10.1007/s11302-024-10053-8","DOIUrl":"https://doi.org/10.1007/s11302-024-10053-8","url":null,"abstract":"Purine nucleotides and nucleosides play critical roles in various pathological conditions, including tumor cell growth. Adenosine triphosphate (ATP) activates pro-tumor receptors, while adenosine (ADO) is a potent immunosuppressant and modulator of cell growth. This study aims to analyze the purinergic actions of ATP and its metabolites, associated enzymes, and P1 or P2 class receptors in primary central nervous system tumors. Additionally, we sought to correlate the levels of nucleosides and the density of P1, P2X, and P2Y receptors in cells with tumor progression. The results indicate that purinergic signaling depends on the receptor concentration and signaling molecules specific to each cell type, tissue, and tumor histology. The purinergic system may function as either a tumor-promoting agent or an antitumor factor, depending on the microenvironmental conditions and the concentrations of receptors and their respective activators. Notably, ATP emerges as the most significant extracellular signal, capable of being converted into other cellular stimulators pertinent to neoplasms, such as adenosine diphosphate, adenosine monophosphate, adenosine, and inosine. Consequently, a cascade of responses to these stimuli promotes tumor development, cell division, and metastasis. Purine nucleotides in central nervous system tumors are pivotal in cellular responses in glioblastoma multiforme, vestibular schwannoma, medulloblastoma, adenomas, gliomas, meningiomas, and pineal tumors. These findings hold the potential for developing novel therapeutic strategies and aiding in therapeutic management.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical and clinical aspects of P2X receptors as a common route in different diseases: A meeting report. P2X 受体作为不同疾病共同途径的临床前和临床方面：会议报告。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-02-20 DOI: 10.1007/s11302-024-09994-x

Luke Tattersall, Elena Adinolfi, Luca Antonioli, Ankita Agrawal

引用次数: 0

Regulation of nerve-evoked contractions of the murine vas deferens. 神经诱发小鼠输精管收缩的调节。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-02-20 DOI: 10.1007/s11302-024-09993-y

Pei Yee Wong, Zhihui Fong, Mark A Hollywood, Keith D Thornbury, Gerard P Sergeant

{"title":"Regulation of nerve-evoked contractions of the murine vas deferens.","authors":"Pei Yee Wong, Zhihui Fong, Mark A Hollywood, Keith D Thornbury, Gerard P Sergeant","doi":"10.1007/s11302-024-09993-y","DOIUrl":"10.1007/s11302-024-09993-y","url":null,"abstract":"Stimulation of sympathetic nerves in the vas deferens yields biphasic contractions consisting of a rapid transient component resulting from activation of P2X1 receptors by ATP and a secondary sustained component mediated by activation of α1-adrenoceptors by noradrenaline. Noradrenaline can also potentiate the ATP-dependent contractions of the vas deferens, but the mechanisms underlying this effect are unclear. The purpose of the present study was to investigate the mechanisms underlying potentiation of transient contractions of the vas deferens induced by activation of α1-adrenoceptors. Contractions of the mouse vas deferens were induced by electric field stimulation (EFS). Delivery of brief (1s duration) pulses (4 Hz) yielded transient contractions that were inhibited tetrodotoxin (100 nM) and guanethidine (10 µM). α,β-meATP (10 µM), a P2X1R desensitising agent, reduced the amplitude of these responses by 65% and prazosin (100 nM), an α1-adrenoceptor antagonist, decreased mean contraction amplitude by 69%. Stimulation of α1-adrenoceptors with phenylephrine (3 µM) enhanced EFS and ATP-induced contractions and these effects were mimicked by the phorbol ester PDBu (1 µM), which activates PKC. The PKC inhibitor GF109203X (1 µM) prevented the stimulatory effects of PDBu on ATP-induced contractions of the vas deferens but only reduced the stimulatory effects of phenylephrine by 40%. PDBu increased the amplitude of ATP-induced currents recorded from freshly isolated vas deferens myocytes and HEK-293 cells expressing human P2X1Rs by 93%. This study indicates that: (1) potentiation of ATP-evoked contractions of the mouse vas deferens by α1-adrenoceptor activation were not fully blocked by the PKC inhibitor GF109203X and (2) that the stimulatory effect of PKC on ATP-induced contractions of the vas deferens is associated with enhanced P2X1R currents in vas deferens myocytes.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"547-557"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906394","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}

引用次数: 0

Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A₃ adenosine receptor in HL-60 cells. 激动剂 MRS5698 和异位增强剂 LUF6000 对 HL-60 细胞中原生 A3 腺苷受体的遗传和功能调节。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-02-28 DOI: 10.1007/s11302-024-09992-z

Zhan-Guo Gao, Weiping Chen, Ray R Gao, Jonathan Li, Dilip K Tosh, John A Hanover, Kenneth A Jacobson

{"title":"Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells.","authors":"Zhan-Guo Gao, Weiping Chen, Ray R Gao, Jonathan Li, Dilip K Tosh, John A Hanover, Kenneth A Jacobson","doi":"10.1007/s11302-024-09992-z","DOIUrl":"10.1007/s11302-024-09992-z","url":null,"abstract":"The A3 adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A3AR agonist MRS5698, positive allosteric modulator (PAM) LUF6000, or both. Both pro- and anti-inflammatory genes, such as IL-1a, IL-1β, and NFκBIZ, are significantly upregulated. During our observations, LUF6000 alone produced a lesser effect, while the MRS5698 + LUF6000 group demonstrated generally greater effects than MRS5698 alone, consistent with allosteric enhancement. The number of genes up- and down-regulated are similar. Pathway analysis highlighted the critical involvement of signaling molecules, including IL-6 and IL-17. Important upstream regulators include IL-1a, IL-1β, TNF-α, NF-κB, etc. PPAR, which modulates eicosanoid metabolism, was highly downregulated by the A3AR agonist. Considering previous pharmacological results and mathematical modeling, LUF6000's small enhancement of genetic upregulation suggested that MRS5698 is a nearly full agonist, which we demonstrated in both cAMP and calcium assays. The smaller effect of LUF6000 on MRS5698 in comparison to its effect on Cl-IB-MECA was shown in both HL-60 cells endogenously expressing the human (h) A3AR and in recombinant hA3AR-expressing CHO cells, consistent with its HL-60 cell genetic regulation patterns. In summary, by using both selective agonists and PAM, we identified genes that are closely relevant to immunity and inflammation to be regulated by A3AR in differentiated HL-60 cells, a cell model of neutrophil function. In addition, we demonstrated the previously uncharacterized allosteric signaling-enhancing effect of LUF6000 in cells endogenously expressing the hA3AR.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"559-570"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983636","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}

引用次数: 0

Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells. 用于 LNP 介导的 P2X7siRNA 抑制乳腺癌细胞迁移并诱导其凋亡的新型可离子化脂质合成物。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-03-04 DOI: 10.1007/s11302-024-09989-8

Seyed Hossein Kiaie, Ali Rajabi Zangi, Mohammad Sheibani, Salar Hemmati, Behzad Baradaran, Hadi Valizadeh

{"title":"Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells.","authors":"Seyed Hossein Kiaie, Ali Rajabi Zangi, Mohammad Sheibani, Salar Hemmati, Behzad Baradaran, Hadi Valizadeh","doi":"10.1007/s11302-024-09989-8","DOIUrl":"10.1007/s11302-024-09989-8","url":null,"abstract":"The development of ionizable lipid (IL) was necessary to enable the effective formulation of small interfering RNA (siRNA) to inhibit P2X7 receptors (P2X7R), a key player in tumor proliferation, apoptosis, and metastasis. In this way, the synthesis and utility of IL for enhancing cellular uptake of lipid nanoparticles (LNP) improve the proper delivery of siRNA-LNPs for knockdown overexpression of P2X7R. Therefore, to evaluate the impact of P2X7 knockdown on breast cancer (BC) migration and apoptosis, a branched and synthesized ionizable lipid (SIL) was performed for efficient transfection of LNP with siRNA for targeting P2X7 receptors (siP2X7) in mouse 4T-1 cells. Following synthesis and structural analysis of SIL, excellent characterization of the LNP was achieved (Z-average 126.8 nm, zeta-potential - 12.33, PDI 0.16, and encapsulation efficiency 85.35%). Afterward, the stability of the LNP was evaluated through an analysis of the leftover composition, and toxic concentration values for SIL and siP2X7 were determined. Furthermore, siP2X7-LNP cellular uptake in the formulation was assessed via confocal microscopy. Following determining the optimal dose (45 pmol), wound healing analysis was assessed using scratch assay microscopy, and apoptosis was evaluated using flow cytometry. The use of the innovative branched SIL in the formulation of siP2X7-LNP resulted in significant inhibition of migration and induction of apoptosis in 4T-1 cells due to improved cellular uptake. Subsequently, the innovative SIL represents a critical role in efficiently delivering siRNA against murine triple-negative breast cancer cells (TNBC) using LNP formulation, resulting in significant efficacy.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"533-546"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022519","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}

引用次数: 0

Implications of COVID-19 in Parkinson's disease: the purinergic system in a therapeutic-target perspective to diminish neurodegeneration. COVID-19 对帕金森病的影响：从治疗目标角度看嘌呤能系统，以减少神经变性。

IF 3 4区医学

Purinergic Signalling Pub Date : 2024-10-01 Epub Date: 2024-03-09 DOI: 10.1007/s11302-024-09998-7

Júlia Leão Batista Simões, Geórgia de Carvalho Braga, Samantha Webler Eichler, Gilnei Bruno da Silva, Margarete Dulce Bagatini

{"title":"Implications of COVID-19 in Parkinson's disease: the purinergic system in a therapeutic-target perspective to diminish neurodegeneration.","authors":"Júlia Leão Batista Simões, Geórgia de Carvalho Braga, Samantha Webler Eichler, Gilnei Bruno da Silva, Margarete Dulce Bagatini","doi":"10.1007/s11302-024-09998-7","DOIUrl":"10.1007/s11302-024-09998-7","url":null,"abstract":"The pathophysiology of Parkinson's disease (PD) is marked by degeneration of dopaminergic neurons in the substantia nigra. With advent of COVID-19, which is closely associated with generalized inflammation and multiple organ dysfunctions, the PD patients may develop severe conditions of disease leading to exacerbated degeneration. This condition is caused by the excessive release of pro-inflammatory markers, called cytokine storm, that is capable of triggering neurodegenerative conditions by affecting the blood-brain barrier (BBB). A possible SARS-CoV-2 infection, in serious cases, may compromise the immune system by triggering a hyperstimulation of the neuroimmune response, similar to the pathological processes found in PD. From this perspective, the inflammatory scenario triggers oxidative stress and, consequently, cellular dysfunction in the nervous tissue. The P2X7R seems to be the key mediator of the neuroinflammatory process, as it acts by increasing the concentration of ATP, allowing the influx of Ca2+ and the occurrence of mutations in the α-synuclein protein, causing activation of this receptor. Thus, modulation of the purinergic system may have therapeutic potential on the effects of PD, as well as on the damage caused by inflammation of the BBB, which may be able to mitigate the neurodegeneration caused by diseases. Considering all the processes of neuroinflammation, oxidative stress, and mitochondrial dysfunction that PD propose, we can conclude that the P2X7 antagonist acts in the prevention of viral diseases, and it also controls purinergic receptors formed by multi-target compounds directed to self-amplification circuits and, therefore, may be a viable strategy to obtain the desired disease-modifying effect. Thus, purinergic system receptor modulations have a high therapeutic potential for neurodegenerative diseases such as PD.","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"487-507"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068663","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}

引用次数: 0