INPP5D调节人体微质中的炎症酶激活
Vicky Chou1, Richard V Pearse1, Aimee J Aylward1
1Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nature communications
|November 28, 2023
概括
通过激活NLRP3炎症体,微质中的降低伊诺西聚酸-5-酸酶D (INPP5D) 活性驱动阿尔茨海默病 (AD) 神经炎症. 这突出了INPP5D作为AD的潜在治疗点.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 微细胞和神经炎症是阿尔茨海默氏症 (AD) 病原发生的关键.
- 伊诺西聚酸-5-酸酶D (INPP5D/SHIP1),是一种髓质表达基因,与AD风险有遗传联系.
研究的目的:
- 研究INPP5D通过哪些分子机制影响AD中的微质功能.
- 探索INPP5D在神经炎症中的作用及其与AD的关联.
主要方法:
- 无偏见的RNA和INPP5D破坏的iPSC衍生的人类微质蛋白的蛋白质概况.
- 对INPP5D在炎症组分上的活性进行药理学验证.
- 对阿兹海默症患者和对照组的人类大脑组织的多分析检查.
主要成果:
- 减少INPP5D活动与破坏的自和炎症酶激活相关.
- 药理上抑制INPP5D促进了NLRP3炎症酶组合,CASP1分裂和IL-1β/IL-18分泌.
- 人类微质中的INPP5D功能减少与AD大脑中的炎症酶激活有关.
结论:
- 微质中的INPP5D活性降低通过炎症酶激活促进AD病原发生.
- 准炎症酶途径为阿尔茨海默病提供了潜在的治疗策略,特别是在INPP5D功能受损的个体中.
相关概念视频
The JAK-STAT Signaling Pathway
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...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...


