在骨关节炎中,通过内分泌网膜应激应激来调节状细胞亡
1Taizhou Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu Province, China; The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, China.
Cell stress & chaperones
|November 8, 2024
概括
细胞内膜网膜应激 (ERS) 在骨关节炎 (OA) 中驱动慢性细胞亡. 针对ESR途径提供了一种新的治疗策略,用于管理OA进展和改善关节健康.
科学领域:
- 生物医学科学 生物医学科学
- 分子生物学分子生物学
- 病理生理学 病理生理学
背景情况:
- 骨关节炎 (OA) 是一种退行性关节疾病,其特征是慢性细胞亡.
- 细胞内膜网膜应激 (ERS) 是OA发病的一个关键因素,破坏细胞平衡.
- 展开的蛋白质反应 (UPR) 试图恢复ER平衡,但长时间的ERS会触发亡.
研究的目的:
- 审查OA中ERS诱导的亡机制.
- 为了确定关键的目标和监管途径,涉及到ERS介导的冠状细胞死亡.
- 探索针对OA治疗的ERS的治疗策略.
主要方法:
- 在OA中对ERS,UPR和冠状细胞亡的研究的文献综述.
- 分析将ERS与亡信号传递联系起来的分子机制.
- 汇编有关ERS相关药物标和OA化合物的数据.
主要成果:
- 长时间的ERS压倒了适应性UPR机制,导致了状细胞亡.
- 特定的ERS信号通路和亡因子与OA进展有关.
- 几种与ERS相关的药物和化合物显示出对关节炎治疗的潜力.
结论:
- 控制ERS及其亡因子对预防和治疗OA至关重要.
- 了解ERS诱导的亡机制为新的治疗干预提供了洞察力.
- 针对ERS途径是未来OA疗法的一个有希望的途径.
相关概念视频
Regulation of the Unfolded Protein Response
2.4K
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...
2.4K
Export of Misfolded Proteins out of the ER
3.5K
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...
3.5K
Role of ER in the Secretory Pathway
5.3K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.3K
Apoptosis
11.2K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.2K
The Unfolded Protein Response
4.4K
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...
4.4K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K


