相关实验视频
Updated: Jun 1, 2025

10:34
A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
7.6K
功能障碍的BCAA降解会通过因PP2Ac相互作用增强而破坏的AMPK-线粒体轴引发神经元损伤
Shih-Cheng Wu1,2, Yan-Jhen Chen3,4, Shih-Han Su5
1Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 10048, Taiwan. shihchengwu@ntu.edu.tw.
Communications biology
|January 21, 2025
概括
增加的分支链氨基酸 (BCAA) 通过降低神经元AMP激活蛋白激酶 (AMPK) 活性来破坏大脑功能,损害自并导致氧化损伤. 这将代谢失衡与神经功能障碍联系在一起.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 代谢和神经系统疾病通常涉及分支链氨基酸 (BCAA) 代谢功能障碍.
- 将BCAA失衡与神经损伤联系在一起的确切机制尚不清楚.
研究的目的:
- 为了研究BCAA代谢缺陷如何导致神经功能障碍.
- 阐明连接BCAA不平衡与神经元损伤的分子通路.
主要方法:
- 产生具有受损BCAA代谢能力的Drosophila突变体.
- 对BCAA水平,神经元AMPK活性和自的分析.
- 研究线粒体的活性氧物种 (ROS) 和蛋白质相互作用.
主要成果:
- 突变者表现出高水平的BCAA,神经功能障碍和神经元AMPK活性降低.
- 抑制AMPK导致自断,并加剧了线粒体功能障碍.
- 过量的BCAA诱导ROS,导致PP2Ac与AMPK结合并抑制其活性.
结论:
- BCAA失衡是通过AMPK抑制和自干扰的神经元损伤的关键驱动因素.
- 这项研究揭示了神经疾病中AMPK和线粒体之间的新反循环.
- 研究结果提供了对新陈代谢-神经元相互作用和神经疾病潜在治疗点的见解.
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.1K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.1K
The Proteasome
805
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
805
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
Amyloid Fibrils
9.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.2K
ATP Synthase: Mechanism
13.9K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
13.9K
Muscle Recovery and Fatigue
1.9K
Muscle fatigue refers to the decline in a muscle's ability to maintain the force of contraction after prolonged activity. It primarily stems from changes within muscle fibers. Even before experiencing muscle fatigue, one may feel tired and have the urge to stop the activity. This response, known as central fatigue, occurs due to changes in the central nervous system, namely the brain and spinal cord. While there is no single mechanism that induces fatigue, it may serve as a protective...
1.9K

