相关实验视频

Updated: May 11, 2026

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Published on: May 16, 2017

在C9ORF72-ALS/FTD小鼠模型中,DDX3X过度表达降低了二重复蛋白

Xiujuan Fu¹, Zhe Zhang¹, Lindsey R Hayes²

¹Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Experimental neurology

|March 31, 2024

概括

在小鼠中过度表达DEAD-box化酶3X结合 (DDX3X) 减少了与C9ORF72-ALS/FTD相关的有毒二重复蛋白,但不会造成伤害. 这表明DDX3X是这些神经退行性疾病的潜在治疗点.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

C9ORF72重复扩张导致ALS和FTD.
从RAN翻译中生成的二重复蛋白 (DPR) 是有毒的.
减少DPR是C9ORF72-ALS/FTD的治疗目标.

研究的目的:

在C9ORF72-ALS/FTD的小鼠模型中评估DDX3X过度表达的体内疗效.
确定DDX3X是否降低了中枢神经系统 (CNS) 中的DPR水平和相关病理.

主要方法:

腺相关病毒血清型9 (AAV9) 将外源的DDX3X或GFP输入C9-BAC转基因小鼠的中枢神经系统.
在分娩12个月后评估DPR水平,p62聚合,神经元损失和神经炎症.

主要成果:

在C9-BAC小鼠的大脑中,DDX3X过度表达显著降低了DPR水平.
在DDX3X治疗的小鼠中,p62聚合也降低了.
没有发现神经元损失或神经炎症的证据.

结论:

在C9ORF72-ALS/FTD小鼠模型中,DDX3X过度表达有效降低了体内DPR水平.
这种方法没有诱导神经毒性或神经炎症.
增加DDX3X表达是C9ORF72-ALS/FTD的一个有前途的治疗策略.

关键词:

这就是ALS.C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C 这是一个FTD.重复扩张的扩张.

更多相关视频

Measuring RAN Peptide Toxicity in C. elegans

Measuring RAN Peptide Toxicity in C. elegans

Published on: April 30, 2020

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

相关概念视频

Huntington Disease l: Introduction

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...