核酸逆转录酶抑制剂具有内在的抗炎活性
Benjamin J Fowler1, Bradley D Gelfand2, Younghee Kim3
1Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA. Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
概括
核酸逆转录酶抑制剂 (NRTIs) 重新用于P2X7驱动的疾病. 这些艾滋病毒药物抑制了炎症酶激活,在地理缩和炎症模型中显示出有效性.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 眼科医生 眼科 眼科
背景情况:
- 核酸逆转录酶抑制剂 (NRTIs) 是抑制病毒复制的关键HIV治疗方法.
- 阿鲁RNA激活P2X7和NLRP3炎症酶,导致视网膜细胞死亡在地理缩,与年龄相关的黄斑变性的一种形式.
研究的目的:
- 研究NRTI在治疗P2X7驱动的炎症性疾病中的潜力.
- 为了确定NRTI是否可以抑制NLRP3炎症酶激活,独立于它们的抗病毒活性.
主要方法:
- 评估了由 Alu RNA 诱导的 P2X7 介导的 NLRP3 炎症酶激活的 NRTI 抑制.
- 评估了caspase-1激活作为炎症酶活动的读数.
- 在地理缩,冠状腺新血管化,移植对宿主疾病和无菌肝炎的小鼠模型中测试了NRTI的疗效.
主要成果:
- NRTI有效地抑制了由P2X7介导的NLRP3炎症酶激活和由AluRNA诱导的caspase-1裂变.
- 这种抑制是独立于逆转录酶抑制的.
- 在多种炎症性疾病的临床前模型中,NRTI证明了治疗效果.
结论:
- 通过抑制P2X7-NLRP3炎症体通路,NRTI具有强大的抗炎性质.
- 对NRTI的药物重新定位是治疗P2X7驱动的炎症疾病,包括地理缩的有希望的策略.
相关概念视频
Inhibitors of Viral Protein Synthesis
47
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
47
siRNA - Small Interfering RNAs
19.2K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
19.2K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
832
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
832
Inhibitors of Bacterial DNA Synthesis
97
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
97
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
740
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
740
Drugs for Treatment of Ulcerative Colitis in IBD
684
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
684


