一种由蛋白酶激活受体衍生的双对应模仿了激活蛋白C的神经元抗亡活性
Abhay Sagare1,2, Youbin Kim1,2, Kassandra Kisler1,2
1Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Bioengineering (Basel, Switzerland)
|September 27, 2025
概括
来自蛋白酶激活受体 (PAR) 的G10模仿了激活蛋白C (APC) 在神经元中的抗亡作用. 这种复制了APC的关键细胞保护功能,表明了治疗潜力.
科学领域:
- 生物化学和分子生物学
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 活性蛋白C (APC) 具有重要的抗凝固和细胞保护功能.
- APC信号涉及蛋白酶激活受体 (PARs),产生激活偏向G蛋白结合受体 (GPCRs) 的.
- 这些GPCRs调解抗炎,抗亡和内皮屏障稳定活动.
研究的目的:
- 为了调查G10,一种PAR衍生激素,是否复制APC的抗亡活性.
- 评估G10在保护培养的小鼠神经元免受N-甲基-d-阿斯巴酸诱导的亡中的有效性.
主要方法:
- 利用培养的小鼠神经元作为模型系统.
- 使用N-甲基-d-酸盐 (NMDA) 诱导的神经细胞亡的挑战.
- 用G10来评估其神经保护作用.
主要成果:
- G10在小鼠神经元中表现出显著的抗亡活性.
- 这一发现表明G10有效地模仿APC的抗亡信号传递.
- G10复制了APC的三个主要细胞保护性活动:抗炎,抗亡和内皮屏障稳定.
结论:
- 来自PAR的G10是一种强大的模仿APC的细胞保护信号.
- G10显示出作为各种病理的潜在治疗剂的前景.
- 需要对G10进行进一步的研究,以其他基于的GPCR激动剂的成功为基础.
相关概念视频
The Intrinsic Apoptotic Pathway
8.3K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.3K
Caspases
13.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
13.7K
The Extrinsic Apoptotic Pathway
8.1K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
8.1K
Enzyme-linked Receptors
86.0K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
86.0K
Phagocytosis of Apoptotic Cells
4.9K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
4.9K
Apoptosis
14.1K
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...
14.1K


