相关实验视频

Updated: Jul 20, 2025

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Published on: February 12, 2015

在A型FTLD-TDP中,TDP-43形成有明显折叠的粉状纤维

Diana Arseni¹, Renren Chen¹, Alexey G Murzin¹

¹MRC Laboratory of Molecular Biology, Cambridge, UK.

|August 2, 2023

概括

异常的TARDNA结合蛋白43 (TDP-43) 会导致神经退行性疾病,如ALS和FTLD. 研究人员在A型FTLD-TDP中发现了一种新的TDP-43丝结构,与ALS和B型FTLD-TDP不同.

科学领域:

神经科学
结构生物学
生物化学

背景情况:

TAR DNA 结合蛋白 43 (TDP-43) 的异常组合是肌缩侧面硬化 (ALS) 和前叶退化 (FTLD) 的标志.
在TARDBP基因突变促进TDP-43组装,因果链接到ALS和FTLD.
根据TDP-43的分布和临床表现,定义了四种具有TDP-43病理性的FTLD (FTLD-TDP).

研究的目的:

在A型FTLD-TDP中确定组装的TDP-43的结构.
将这些结构与ALS和B型FTLD-TDP中发现的结构进行比较.
确定可能影响TDP-43组装的翻译后修改.

主要方法:

使用冷电子显微镜从A型FTLD-TDP患者的大脑样本中确定组装的TDP-43的结构.
用质谱测量来确定翻译后的修改.
进行了结构分析,以比较不同神经退行性疾病中的TDP-43折叠.

主要成果:

在A型FTLD-TDP中,TDP-43形成了粉样纤维,具有新型的章状折叠,在个体中一致.
这种折叠与ALS和B型FTLD-TDP中观察到的双螺旋折叠不同,表明条件特定的结构.
在组装的TDP-43上发现了两种新的翻译后修饰,即R293的素化和单甲基化.

结论:

不同的TDP-43丝结构是不同神经退行性疾病的特征.
在A型FTLD-TDP中新发现的折叠可能是诊断标志物.
翻译后的修改可能在TDP-43线索形成和结构变异性中起作用,提供治疗点.

更多相关视频

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy

Published on: November 30, 2018

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

相关概念视频

Amyloid Fibrils

Amyloid Fibrils

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,...

Protein Folding

Protein Folding

Formation of Intermediate Filaments

Formation of Intermediate Filaments

Intermediate filaments are cytoskeletal proteins with higher tensile strength and flexibility than microfilaments and microtubules. Unlike the other two cytoskeletal proteins, intermediate filament formation lacks the enzymatic activity to hydrolyze nucleotides like ATP and GTP to generate energy for polymerization. Therefore, the formation of intermediate filaments is multistep self-assembly. The involvement of any accessory proteins in intermediate filament formation has not yet been...