在前叶退化中TAF15粉丝丝
Stephan Tetter1, Diana Arseni1, Alexey G Murzin1
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature
|December 6, 2023
概括
前叶退化 (FTLD) 与异常的蛋白质沉积有关. 研究人员在FTLD-FUS病例中发现了TATA结合蛋白相关因子15 (TAF15) 的粉样纤维,而不是FUS,这显示出一种新的蛋白病变.
科学领域:
- 神经科学
- 生物化学
- 结构生物学
背景情况:
- 前叶退化 (FTLD) 是一种常见的痴呆亚型,其特征是神经元中异常的蛋白质入.
- 虽然TDP-43和tau是已知的FTLD蛋白质,但大约10%的病例 (FTLD-FUS) 涉及Fused in Sarcoma (FUS) 蛋白质,尽管其结构仍未得到证实.
- 了解FTLD-FUS的分子基础对于诊断和治疗这种神经退行性疾病至关重要.
研究的目的:
- 在FTLD-FUS情况下确定粉样纤维的结构特征.
- 研究FUS及其同类在FTLD-FUS病变中的作用.
- 在神经退行性疾病中确定TAF15蛋白质病变的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来分析从FTLD-FUS患者的大脑中分离出来的粉状纤维.
- 确定粉体纤维的结构确定.
- 分析受影响大脑区域的蛋白质组成,包括运动皮层和脑干.
主要成果:
- 在FTLD-FUS患者中,冷EM检测显示大量由TATA结合蛋白相关因子15 (TAF15) 组成的粉样纤维.
- 在所有分析的个体中,TAF15丝体表现出由其低复杂性域 (LCD) 的7 - 99残留物形成的一致结构.
- 在患有运动神经元病理的患者的运动皮质和脑干中发现了相同的TAF15丝结构,证实了TAF15的参与.
结论:
- 该研究确定TAF15是FTLD-FUS中的粉样纤维的主要组成部分,从而确定TAF15蛋白病变.
- 确定TAF15粉状纤维的结构为开发诊断和治疗策略提供了基础.
- 这一发现为研究FTLD和相关神经退行性疾病创造了新的模式.
更多相关视频
10:04Imaging Amyloid Tissues Stained with Luminescent Conjugated Oligothiophenes by Hyperspectral Confocal Microscopy and Fluorescence Lifetime Imaging
Published on: October 20, 2017
13.5K
12:28Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
17.4K
相关概念视频
03:03Amyloid Fibrils
9.6K
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,...
9.6K
01:26Alzheimer's Disease: Overview
494
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...
494