在家族性和零星性肌缩性侧面硬化症中TDP-43突变
Jemeen Sreedharan1, Ian P Blair, Vineeta B Tripathi
1Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, and Institute of Psychiatry, London, SE5 8AF, UK.
Science (New York, N.Y.)
|March 1, 2008
概括
编码TARDNA结合蛋白 (TDP-43) 的TARDBP基因的突变与肌缩性侧面硬化症 (ALS) 有关. 这项研究提供了证据表明,TDP-43功能障碍有助于ALS的神经退行.
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:
- 肌缩侧面硬化症 (ALS) 是一种致命的神经退行性疾病.
- 病理性ALS的特征包括含有无处不在的TARDNA结合蛋白 (TDP-43).
- 目前尚不完全了解TDP-43的确切功能及其在ALS病变中的作用.
研究的目的:
- 调查TARDBP突变在ALS中的潜在作用.
- 为了探索TDP-43突变的功能后果.
主要方法:
- 零星和家族ALS病例的遗传分析以确定TARDBP突变.
- 在发现突变的家族内进行分离分析.
- 全基因组链接扫描以确认基因位置.
- 突变TDP-43碎片化的体外研究.
- 使用胚胎模型进行体内研究,以评估神经亡和发育影响.
主要成果:
- 在ALS患者中,在TARDBP的保存区域中发现了邻近突变.
- 一个特定的突变,TARDBPM337V,与疾病分离在一个亲属.
- 联系分析证实了TARDBP位点在1p36.6染色体上的位置.
- 与野生类型相比,突变TDP-43在体外显示出更多的碎片化.
- 在体内,突变TDP-43诱导了胚胎的神经亡和发育延迟.
结论:
- 这些发现表明,TDP-43功能障碍与ALS之间存在直接的病理生理联系.
- 在TARDBP的突变有助于ALS的神经退行过程.
- TDP-43在神经元健康和发育中发挥着关键作用,其功能障碍可能导致ALS.
更多相关视频
13:31Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis
Published on: February 12, 2015
06:58Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
相关概念视频
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:21Huntington 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,...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
03:03Amyloid 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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...