{"title":"探索PI3K/AKT/mTOR和JNK信号通路在银屑病中的相互作用:来自系统评价和网络药理学方法的见解","authors":"Ali Ebrahimi, Pantea Mohammadi, Seyedeh Zahra Mirzaei, Elisa Zavattaro, Masoud Sadeghi, Masomeh Mehrabi, Sasan Shabani, Samira Ranjbar, Reza Khodarahmi","doi":"10.2174/0113892010380506250909114143","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. Central to its pathogenesis are the PI3K/AKT/mTOR and JNK signaling pathways, which regulate inflammation and keratinocyte behavior.</p><p><strong>Methods: </strong>This study reviewed experimental data reported in the scientific literature and utilized network pharmacology to investigate the interplay between the PI3K/AKT/mTOR and JNK pathways, aiming to elucidate the underlying mechanisms of psoriasis. 709 records from Scopus, Web of Sciences, Cochrane Library and PubMed were reviewed without limitations until October 3, 2023. 85 articles were included in the systematic review.</p><p><strong>Results: </strong>Key molecules, including EGFR, Sortilin, and Cyr61, were identified as important links between these pathways, influencing cell survival and apoptosis. Flavonoids such as Rhododendrin, Erianin, and Fisetin were found to effectively target both of these pathways, potentially modifying cellular behavior and offering therapeutic benefits. The network analysis revealed that EGFR and AKT serve as critical connectors between hub genes CDC42 and GAPDH, with these flavonoids impacting downstream signaling molecules, including PI3K, AKT, mTOR, Grb2, JAK, STAT, Cyclooxygenase, HIF-1α, and MAPKs.</p><p><strong>Discussion: </strong>The findings highlight the pivotal role of the PI3K/AKT/mTOR pathway in promoting inflammation and cellular proliferation by activating NF-κB and HIF-1α.</p><p><strong>Conclusion: </strong>This comprehensive review underscores the importance of the PI3K/AKT/mTOR and JNK pathways in understanding psoriasis mechanisms. Targeting these pathways with flavonoids may offer promising therapeutic strategies by modulating key molecular hubs involved in disease progression.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the Interplay of PI3K/AKT/mTOR and JNK Signaling Pathways in Psoriasis: Insights from Systematic Review and Network Pharmacology Approach.\",\"authors\":\"Ali Ebrahimi, Pantea Mohammadi, Seyedeh Zahra Mirzaei, Elisa Zavattaro, Masoud Sadeghi, Masomeh Mehrabi, Sasan Shabani, Samira Ranjbar, Reza Khodarahmi\",\"doi\":\"10.2174/0113892010380506250909114143\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. 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引用次数: 0
摘要
简介:银屑病是一种慢性炎症性皮肤病,以角化细胞过度增殖、分化异常、炎症细胞浸润为特征。其发病机制的核心是PI3K/AKT/mTOR和JNK信号通路,它们调节炎症和角化细胞的行为。方法:本研究通过查阅科学文献中的实验数据,利用网络药理学方法研究PI3K/AKT/mTOR和JNK通路的相互作用,旨在阐明银屑病的潜在机制。截至2023年10月3日,对Scopus、Web of Sciences、Cochrane Library和PubMed的709条记录进行了无限制的综述。85篇文章被纳入系统评价。结果:发现EGFR、Sortilin、Cyr61等关键分子是这些通路之间的重要环节,影响细胞存活和凋亡。类黄酮如杜鹃花素、鸢尾素和非瑟酮被发现有效地靶向这两种途径,潜在地改变细胞行为并提供治疗益处。网络分析显示,EGFR和AKT是枢纽基因CDC42和GAPDH之间的关键连接物,这些类黄酮影响下游信号分子,包括PI3K、AKT、mTOR、Grb2、JAK、STAT、环氧合酶、HIF-1α和MAPKs。讨论:这些发现强调了PI3K/AKT/mTOR通路通过激活NF-κB和HIF-1α在促进炎症和细胞增殖中的关键作用。结论:这项综合综述强调了PI3K/AKT/mTOR和JNK通路在理解银屑病机制中的重要性。用类黄酮靶向这些途径可能通过调节参与疾病进展的关键分子枢纽提供有希望的治疗策略。
Exploring the Interplay of PI3K/AKT/mTOR and JNK Signaling Pathways in Psoriasis: Insights from Systematic Review and Network Pharmacology Approach.
Introduction: Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. Central to its pathogenesis are the PI3K/AKT/mTOR and JNK signaling pathways, which regulate inflammation and keratinocyte behavior.
Methods: This study reviewed experimental data reported in the scientific literature and utilized network pharmacology to investigate the interplay between the PI3K/AKT/mTOR and JNK pathways, aiming to elucidate the underlying mechanisms of psoriasis. 709 records from Scopus, Web of Sciences, Cochrane Library and PubMed were reviewed without limitations until October 3, 2023. 85 articles were included in the systematic review.
Results: Key molecules, including EGFR, Sortilin, and Cyr61, were identified as important links between these pathways, influencing cell survival and apoptosis. Flavonoids such as Rhododendrin, Erianin, and Fisetin were found to effectively target both of these pathways, potentially modifying cellular behavior and offering therapeutic benefits. The network analysis revealed that EGFR and AKT serve as critical connectors between hub genes CDC42 and GAPDH, with these flavonoids impacting downstream signaling molecules, including PI3K, AKT, mTOR, Grb2, JAK, STAT, Cyclooxygenase, HIF-1α, and MAPKs.
Discussion: The findings highlight the pivotal role of the PI3K/AKT/mTOR pathway in promoting inflammation and cellular proliferation by activating NF-κB and HIF-1α.
Conclusion: This comprehensive review underscores the importance of the PI3K/AKT/mTOR and JNK pathways in understanding psoriasis mechanisms. Targeting these pathways with flavonoids may offer promising therapeutic strategies by modulating key molecular hubs involved in disease progression.
期刊介绍:
Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include:
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Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.