在TDP-43错位化和ALS中疾病严重程度中阿迪波内克丁-AMPK轴的作用
Yu-Ju Liu1, Chia-Wei Lee1, Yi-Chu Liao2
1Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Neurobiology of disease
|November 3, 2024
概括
在ALS患者中,阿迪波涅丁水平升高与疾病严重程度相关. 这表明阿迪波内克丁-AMPK-TDP-43通路可能会导致肌缩侧面硬化症的能量失衡.
科学领域:
- 神经科学是一个神经科学.
- 代谢研究研究 代谢研究
- 细胞生物学 细胞生物学
背景情况:
- 肌缩侧面硬化症 (ALS) 的特点是超高代谢.
- 由阿迪波涅克影响的AMP激活蛋白激酶 (AMPK) 的异常激活与TDP-43错位化有关,这是早期的ALS事件.
研究的目的:
- 研究ALS患者的能量介质和临床严重程度之间的关系.
- 探索阿迪波内克丁-AMPK-TDP-43轴在ALS病变发生中的作用.
主要方法:
- 分析了血腺素水平和肌缩侧面硬化功能评分尺度修订 (ALSFRS-R) 评分.
- 边缘血液单核细胞 (PBMC) 的免疫光染色评估了AMPK激活和TDP-43错位.
- 在体外研究中,NSC34细胞和诱导的多能干细胞衍生的运动神经元 (HiPSC-MNs) 用adiponectin治疗.
主要成果:
- 在ALS患者中观察到更高的血腺素水平,ALSFRS-R得分较低.
- 阿迪波涅克丁度与ALSFRS-R得分呈反向相关性.
- 在运动神经元模型中,阿迪波涅克丁治疗诱导了AMPK激活和TDP-43错位.
结论:
- 血腺素水平升高可能导致AMPK激活和ALS中的TDP-43错位.
- 阿迪波内克丁-AMPK-TDP-43轴与ALS相关的能量失调有关.
- 在运动神经元中,阿迪波涅克丁受体信号传递对这些效应至关重要.
更多相关视频
09:20An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
3.6K
06:58Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
582
相关概念视频
Alzheimer's Disease: Overview
449
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
449
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
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
