蛋白质稳定网络对环境慢性压力的反应:在人类神经母细胞瘤细胞模型中,将生存与蛋白质聚合联系起来
Emiliano Montalesi1, Daniela Caissutti1, Camilla Moliterni1
1Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
Cellular and molecular life sciences : CMLS
|November 27, 2025
概括
慢性压力会破坏细胞蛋白质稳定,增加粉样蛋白负担和TDP-43聚合,这是像ALS这样的神经退行性疾病的关键因素.
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
- 生物化学 生化学
背景情况:
- 蛋白质稳定网络 (PN) 维持细胞蛋白质质量,这对神经元至关重要.
- 皮质核的失调与神经退行性疾病有关.
研究的目的:
- 在慢性压力下调查PN变化.
- 将这些变化与粉样蛋白负担和TDP-43聚合联系起来.
主要方法:
- 神经母细胞瘤SH-SY5Y细胞被环境压力处理.
- 在24小时和72小时后分析PN成分,粉样蛋白负担 (提奥夫拉染),以及TDP-43酸化/不溶性的分析.
主要成果:
- 压力诱导的蛋白酶体损伤,停止了蛋白质合成和自.
- 观察到粉样蛋白负荷增加和化TDP-43 (pTDP-43).
- pTDP-43显示了裂变和增加的不溶性.
结论:
- TDP-43聚合是综合应激反应的核心.
- 改变PN功能驱动神经退行发作.
- 粉样蛋白负担反映了压力下细胞系统的健康状况.
相关概念视频
Other Stress Responses in Bacteria
314
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
314
Regulation of the Unfolded Protein Response
2.9K
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...
2.9K
The Unfolded Protein Response
6.2K
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...
6.2K
Stringent Response in E. coli
267
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
267
Hypothalamic-Pituitary Axis
65.3K
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
65.3K
Protein Networks
4.5K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.5K


