INPP5D/SHIP1是人类微质细胞内内溶酶体功能和选择性细胞分裂的双重调节者
Gizem Terzioglu1, Emma S Karp1, Sarah E Heuer1
1Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
在阿尔茨海默氏症 (AD) 中,SHIP1蛋白通过控制内体和溶体的功能来调节免疫细胞. 它的缺乏会损害炎症反应,促进脂质积累,影响AD的发病性.
科学领域:
- 神经免疫学 神经免疫学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 编码SHIP1的INPP5D基因与阿尔茨海默病 (AD) 风险有关.
- SHIP1对于调节免疫细胞炎症路径至关重要,特别是在微质细胞中.
研究的目的:
- 研究SHIP1抑制人类微质细胞炎症的机制.
- 了解SHIP1在内分体成熟,溶酶体功能和AD病理学中的作用.
主要方法:
- 利用基因组编辑来降低微质中的SHIP1水平.
- 进行了CITE-seq分析,以分析细胞状态.
- 研究了SHIP1局部化和蛋白质相互作用 (CapZ).
主要成果:
- 缺少SHIP1会损害内分体成熟和 lysosomal 功能,导致脂质滴积累.
- 缺少SHIP1的微质体表现出免疫状态的改变,神经元残骸的增强性细胞分解,以及LPS反应的受损.
- 由于缺陷的溶酶体降解,氨基酸β会在细胞内积累,促进脂质的形成和NLRP3炎症酶的激活.
结论:
- SHIP1对于微质细胞的内溶酶功能和选择性细胞化至关重要.
- SHIP1缺陷通过受损的溶酶体降解和改变的微质表型,有助于AD的发病.
- SHIP1代表了阿尔茨海默病,自身免疫性疾病和癌症的潜在治疗标.
相关概念视频
Delivery Pathways to the Lysosome
8.7K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.7K
Phosphoinositides and PIPs
10.0K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.0K
Phagocytosis of Apoptotic Cells
4.9K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
4.9K


