糖原合成酶激酶3抑制可以控制Mycobacterium tuberculosis的感染
Sandra Peña-Díaz1, Joseph D Chao2, Celine Rens2
1Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
iScience
|August 23, 2024
概括
用P-4423632等化合物准糖原合成酶激酶3 (GSK3) 抑制了Mycobacterium结核病的生长. 这种宿主导治疗方法通过增强先天免疫力来治疗传染病具有前景.
科学领域:
- 传染性疾病 传染性疾病
- 主人导向疗法 主人导向疗法
- 分子生物学分子生物学
背景情况:
- 抗菌素耐药性需要新的治疗策略.
- 主体导向疗法提供了一个替代方案,通过准对病原体生存至关重要的宿主途径.
研究的目的:
- 为了识别抑制细胞内Mycobacterium结核病 (Mtb) 增长的宿主向化合物.
- 调查糖原合成酶激酶3 (GSK3) 在Mtb感染中的作用,并探索GSK3抑制剂作为治疗策略.
主要方法:
- 基因酶库的表型查,以确定Mtb生长抑制剂.
- 克里斯普尔淘汰和siRNA沉默来确定GSK3异型的作用.
- 使用化合物P-4423632和蛋白质组分析进行化学抑制.
- 对巨细胞亡和对其他细胞内病原体的活性进行检测.
主要成果:
- GSK3异型对Mtb细胞内生长至关重要.
- 化合物P-4423632专门针对GSK3β,并抑制巨细胞中的Mtb生长.
- 抑制GSK3诱导巨细胞亡,由Mtb的PtpA调节.
- P-4423632对细胞内病原体表现出广泛的活性.
结论:
- 向GSK3代表了一种可行的宿主导治疗传染病的方法.
- -4423632是一种有前途的化合物,用于开发针对细胞内病原体的新疗法.
- 通过信号调制来增强宿主的先天抗菌能力是一种有效的治疗方法.
相关概念视频
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Pulmonary Tuberculosis I
227
Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
227


