通过TRIM16介导的溶解抑制了高葡萄糖累积的神经元Aββ
Chang Woo Chae1, Jee Hyeon Yoon1, Jae Ryong Lim1
1Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 FOUR Future Veterinary Medicine Leading Education & Research Center, Seoul National University, Seoul, South Korea.
Autophagy
|June 26, 2023
概括
这项研究表明,F-box蛋白27 (FBXO27) 调节 lysosomal 功能和粉样β (Aβ) 清除,为阿尔茨海默病 (AD) 提供新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- lysosomal 功能障碍与阿尔茨海默氏症 (AD) 病原发生有关.
- 粉样β (Aβ) 降解受损有助于AD中Aβ斑块的形成.
- 细胞应激途径影响 lysosomal 功能和蛋白质降解.
研究的目的:
- 研究F-box蛋白27 (FBXO27) 在 lysosomal 功能和Aβ 清除中的作用.
- 探索FBXO27影响 lysosomal 途径的分子机制.
- 确定FBXO27是否是AD的潜在治疗点.
主要方法:
- 利用来自AD患者的诱导多能干细胞衍生神经元分化细胞 (iPSC-NDs).
- 采用了FBXO27.27的基因沉默和过度表达技术.
- 评估了溶酶体标志物 (LAMP1),溶酶体膜通透性 (LMP) 和Aβ水平.
- 分析了FBXO27与ESCRT组件和VCP的相互作用.
主要成果:
- 在iPSC-NDs中,FBXO27缺乏会损害 lysosomal 功能和Aβ 降解.
- FBXO27与VCP和ESCRT组件相互作用,影响溶酶体贩运.
- 过度表达FBXO27促进了Aβ清除并恢复了 lysosomal 完整性.
- FBXO27调节了TFEB/TFE3的转录活性,影响了溶酶体生物发生.
结论:
- FBXO27在维持溶酶体平衡和Aβ清除方面发挥着至关重要的作用.
- 准FBXO27可能为阿尔茨海默病提供一种新的治疗策略.
- FBXO27对溶酶体通路的调节为AD治疗提供了一个有前途的途径.
更多相关视频
09:33Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
8.0K
06:43A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
12.2K
相关概念视频
01:22Lysosomal Hydrolases
3.9K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
01:36Delivery Pathways to the Lysosome
6.6K
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...
6.6K