一种ANXA11 P93S变种调节不良TDP-43并导致皮质基综合征
Allison Snyder1, Veronica H Ryan2,3, James Hawrot1
1Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
概括
该ANXA11 P93S变体是致病性,导致皮质底综合征,并影响神经元和微质功能. 细胞模型有效地确定了变异性病原性,有助于基因测试的解释.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 不确定意义的变异 (VUS) 存在诊断挑战.
- 附件A11 (ANXA11) 与肌缩性侧面硬化症/前性痴呆症有关.
- 已确定的ANXA11突变导致蛋白质聚合和TDP-43错位.
研究的目的:
- 确定新型ANXA11 P93S变种的致病性.
- 研究ANXA11突变的表型谱.
- 探索P93S对ANXA11和TDP-43.3的功能影响.
主要方法:
- 临床评估一种皮质基底综合征的相关性.
- 诱导多能干细胞衍生神经元用于功能研究.
- 神经元和微质细胞的多原子分析.
主要成果:
- 证实ANXA11 P93S变种具有致病性.
- P93S导致 lysosome 局部化下降和 TDP-43 错位化与神秘的外因子表达.
- 微质签名表明免疫失调和干扰素途径参与.
结论:
- ANXA11 P93S具有致病性,并扩大了突变谱.
- 神经和微质功能障碍是ANXA11病理生理学的关键.
- 细胞模型对于VUS评估和了解疾病机制非常有价值.
相关概念视频
01:31Translation
141.8K
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...
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...
141.8K
02:18Alternative RNA Splicing
21.1K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.1K