相关实验视频

Updated: Sep 12, 2025

Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells

Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells

Published on: October 4, 2017

聚合易患病原性SOD1变体在肌缩侧面硬化症:从计算基因组学和进化保护的见解

Farah Anjum^1,2, Maha M Bakhuraysah^3,4, Maram Jameel Hulbah^3,4

¹Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia. farahanjum@tu.edu.sa.

Journal of molecular neuroscience : MN

|August 7, 2025

概括

对244个SOD1突变的计算分析揭示了与肌缩侧面硬化症 (ALS) 相关的八种聚合易感变体. 这项研究增强了对ALS发病过程中的SOD1功能障碍的理解,并指导了向治疗.

科学领域:

基因组学就是基因组学.
神经科学是一个神经科学.
生物化学生物化学

背景情况:

肌缩侧面硬化症 (ALS) 是一种致命的神经退行性疾病,原因不明.
SOD1基因的突变与家族性ALS (fALS) 有关,并通过蛋白质错误折叠和聚合引起有毒功能增长.
了解SOD1突变对于ALS病变研究至关重要.

研究的目的:

使用计算工具系统分析244个SOD1误解突变.
为了识别与SOD1错误折叠,聚合和致病性相关的突变.
为提供有关ALS中SOD1功能障碍的机制性见解.

主要方法:

使用了多层计算框架,结合了结构,功能和病原性预测因素.
使用基于序列的 (SIFT,PolyPhen-2,FATHMM) 和结构引导的 (mCSM,PremPS,DynaMut2) 工具.
使用SODA分析和蛋白质-蛋白质相互作用网络评估聚合倾向.

主要成果:

确定了79种破坏SOD1稳定的突变,其中64种被归类为致病性.
确定了八种容易聚合的突变 (D84N,G73C,H72Y,P67A,P67R,P67S,R144G,S60I),包括破坏关键结合残留物的H72Y.
通过网络分析将SOD1与氧化应激和蛋白质稳态通路联系起来.

结论:

计算基因组学有效地识别了ALS中突变驱动的SOD1功能障碍.
对SOD1聚合的机制性见解为开发有针对性的治疗策略提供了基础.
专注于容易聚合的变异可能为ALS治疗提供新的途径.

关键词:

聚合的倾向聚合的倾向肌缩侧面硬化症 (ALS) 是一种疾病.有害的突变有害的突变蛋白质的稳定性蛋白质的稳定性在SOD1中,SOD1是SOD1.结构基因组学结构基因组学

更多相关视频

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Published on: July 16, 2021

Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons

Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons

Published on: January 7, 2019

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,...

Lysosomal Hydrolases

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...

Parkinson's Disease: Overview

Parkinson's Disease: Overview

Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...