相关实验视频

Updated: Jun 18, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

甲基素1和2的过度表达减少了AβO介导的ER压力和N2a APPswe细胞中的亡

Min Kyoung Kam¹, Su-Min Jung², Ga Eun Lee³

¹School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea. s929795@korea.kr.

Cellular and molecular biology (Noisy-le-Grand, France)

|August 4, 2024

概括

米托福辛 (Mfn1和Mfn2) 在阿尔茨海默病模型中降低了粉样β寡合体诱导的毒性和内质网膜应激. 过度表达这些蛋白质也会减少细胞死亡,提供治疗潜力.

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:

阿尔茨海默病 (AD) 是一种常见的神经退行性疾病,其特征是粉样β寡合体 (AβO).
AβO是有毒的,诱导线粒体功能障碍和内质网膜 (ER) 压力.
线粒体融合中的密托素 (Mfn1和Mfn2) 是关键蛋白质,Mfn2也调节了ER功能.

研究的目的:

研究Mfn1和Mfn2在由AβO引起的ER应激中的作用.
确定Mfn1和Mfn2是否可以减轻AβO介导的细胞毒性和细胞亡.

主要方法:

利用了N2a APPswe细胞,一种小鼠神经母细胞瘤细胞系,过度表达了粉样蛋白前体蛋白的瑞典突变.
评估了Aβ暴露后的细胞毒性,ER压力标志物,ER扩张和细胞亡.
研究了Mfn1和Mfn2过度表达对这些参数的影响.

主要成果:

粉样β (Aβ) 暴露导致毒性,上调ER应激蛋白,并在N2a APPswe细胞中引起ER扩张.
过度表达Mfn1和Mfn2显著降低了AβO介导的ER压力.
Mfn1和Mfn2的过度表达也导致治疗细胞的亡减少.

结论:

在AβO毒性的背景下,Mfn1和Mfn2通过减少ER压力和亡来起保护作用.
这些发现表明Mfn1和Mfn2是阿尔茨海默病的潜在治疗点.
需要进一步研究AD病变发生过程中的Mfn1和Mfn2机制.

更多相关视频

Modified Roller Tube Method for Precisely Localized and Repetitive Intermittent Imaging During Long-term Culture of Brain Slices in an Enclosed System

Modified Roller Tube Method for Precisely Localized and Repetitive Intermittent Imaging During Long-term Culture of Brain Slices in an Enclosed System

Published on: December 28, 2017

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)

Published on: January 10, 2025

相关概念视频

The Unfolded Protein Response

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

Regulation of the Unfolded Protein Response

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...