粉样蛋白前体蛋白和C99是人类微质Hv1通道中的子单元,可增强当前和炎症介质释放的作用
Ruiming Zhao1,2,3, Punyanuch Sophanpanichkul1,2,3, Jean Paul Chadarevian4
1Department of Pediatrics, Susan and Henry Samueli College of Health Sciences, University of California Irvine, Irvine, CA 92697.
概括
人类微中的电压关闭质子通道 (Hv1) 是由粉样蛋白前体蛋白 (APP) 和其片段C99.9调节的. 这种相互作用通过改变通道活性和炎症介质释放来影响阿尔茨海默病 (AD) 的神经炎症.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 阿尔茨海默病 (AD) 涉及神经炎症,由过度活化的微质细胞驱动.
- 粉样蛋白前体蛋白 (APP) 处理是AD病变发生的核心.
- 电压关闭的质子通道 (Hv1) 参与微质激活,但它们在AD中的作用尚不清楚.
研究的目的:
- 研究Hv1通道在人类微质中的作用及其与阿尔茨海默病中APP的联系.
- 确定APP及其碎片如何影响HV1通道功能和微质炎症反应.
主要方法:
- 利用人类诱导的多能干细胞衍生的微质细胞 (iMG) 来研究本地HV1通道.
- 使用HEK293T细胞对APP-Hv1相互作用进行详细的生物物理和生物化学分析.
- 进行了共免疫沉和全内反射光显微镜,以确认蛋白质复合体的形成.
主要成果:
- 人类iMG表达功能Hv1通道,与APP协同组装,影响通道活动.
- 通过APP敲击,减少了HV1电流,抑制了细胞因子和反应性氧物种的释放.
- 该APP片段C99显著改变了Hv1通道功能,并与Hv1形成了稳定的复合体.
结论:
- 人类微质中的Hv1通道由APP及其C99片段调节,影响AD中的神经炎症.
- 在C99内APP (E682K,D694N) 中的早期发病的AD突变增强了Hv1通道活性,加剧了神经炎症.
更多相关视频
08:47Author Spotlight: In Vitro Co-Culture Model for Studying Microglia-Neuronal Interactions in Disease Conditions
Published on: July 26, 2024
3.5K
08:07Assessing the Expression of Major Histocompatibility Complex Class I on Primary Murine Hippocampal Neurons by Flow Cytometry
Published on: May 19, 2020
3.9K
相关概念视频
03:03Amyloid Fibrils
11.6K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
11.6K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.8K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.8K