罗斯马林酸对通过调节GRP78/PERK/MANF通路的内毒素诱导的神经元损伤的保护作用
Qian Li1, Jing-Wen Zheng1, Zi-Yao Wang1
1Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Drug design, development and therapy
|January 16, 2025
概括
罗斯马林酸 (RA) 通过抑制GRP78/PERK/MANF通路,改善了患有内毒素诱导脑病变的小鼠的认知功能. 这种天然化合物在治疗神经炎症和认知衰退方面表现有前途.
科学领域:
- 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.
- 细胞生物学 细胞生物学
背景情况:
- 神经元损伤和内质网膜应激 (ERS) 与认知功能障碍有关.
- 由内毒素引起的长期认知功能障碍的确切机制尚未完全理解,这限制了有效的治疗方法.
研究的目的:
- 在内毒素诱导的认知功能障碍的小鼠模型中研究罗斯马林酸 (RA) 对ERS的保护作用.
- 阐明RA对神经元损伤和认知障碍的作用的潜在机制.
主要方法:
- 利用内毒素诱导的认知功能障碍小鼠模型和体外神经元损伤模型.
- 通过行为测试和组织学染色 (HE) 来评估大脑损伤.
- 使用西式涂抹和免疫组织化学 (IHC) 确定蛋白质表达水平 (NeuN,GRP78,PERK,ATF6,IRE1α,MANF);采用分子对接来探索机制.
主要成果:
- 在没有剂量依赖的小鼠中,RA (20和40 mg/kg) 显著改善了认知功能.
- 关节炎治疗降低了海马的PERK水平,并在特定的大脑区域增加了MANF的表达.
- 在体外,RA抑制了LPS诱导的GRP78,PERK和MANF的上调,分子对接表明与GRP78,PERK和IRE1.1直接相互作用.
结论:
- 罗斯马林酸在小鼠中显示出对内毒性相关脑病变和认知功能障碍的保护作用.
- 该机制涉及抑制GRP78/PERK/MANF信号通路.
更多相关视频
08:53Assessing Neuroprotective Effects of Glycyrrhizae Radix et Rhizoma Extract Using a Transient Middle Cerebral Artery Occlusion Mouse Model
Published on: December 9, 2018
7.3K
10:50Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
951
相关概念视频
01:31Regulation 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...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
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...