相关实验视频

Updated: Jun 6, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

在NPC1中研究p.Ala1035Val:对于尼曼-皮克C型疾病的新细胞模型

Hugo David^1,2,3, Jlenia Monfregola⁴, Isaura Ribeiro^5,6,7

¹Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge (INSA, I. P.), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal.

International journal of molecular sciences

|November 27, 2024

概括

尼曼-皮克型C (NPC) 疾病中的p.Ala1035Val变体会损害NPC1蛋白向溶酶体的贩运,类似于p.Ile1061Thr变体. 这种变种,特别是p.Ile858Val SNP,可能会加剧疾病的进展.

科学领域:

细胞生物学细胞生物学
遗传学是一个遗传学.
生物化学生物化学

背景情况:

尼曼-皮克型C (NPC) 是一种由NPC1或NPC2基因突变引起的溶酶体储存障碍 (LSD),影响胆固醇运输.
在西欧,p.Ile1061Thr NPC1变种是常见的,而在葡萄牙和全球,p.Ala1035Val是普遍存在的.

研究的目的:

研究p.Ala1035Val NPC1变体对细胞的影响,特别是与p.Ile858Val单核酸多态 (SNP) 的相互作用.
为了比较p.Ala1035Val和p.Ile1061Thr变体对NPC1蛋白贩运和 lysosomal定位的功能影响.

主要方法:

使用表达光标记NPC1变异的NPC1缺乏ARPE-19细胞创建了特定变异的体外模型.
利用患者衍生的皮肤纤维细胞进行细胞分析.
检查了溶酶体定位和NPC1蛋白贩运途径.

主要成果:

证实了p.Ile1061Thr变体的减少溶酶体贩运.
对于p.Ala1035Val变体,已经证明了 lysosomal trafficking 的受损,当与p.Ile858Val SNP. in cis时,效果更为严重.
与p.Ile1061Thr.相比,p.Ala1035Val观察到类似或更糟糕的溶酶体定位问题.

结论:

这种p.Ala1035Val变体显著影响NPC1蛋白贩运到 lysosomes.
在cis中p.Ala1035Val和p.Ile858Val的同时出现可能会加剧NPC疾病的细胞表型.
这项研究为p.Ala1035Val变体提供了第一个功能性见解,为向的NPC疗法开辟了道路.

关键词:

在ARPE-19中,ARPE-19是ARPE的第一个类型.在NPC1中,NPC1是NPC1.德国Pick类型C的选择细胞模型细胞模型复杂的等位体复杂的等位体.溶酶体储存障碍溶酶体储存障碍 p.Ala1035ValVal的使用情况第1061页通过 p.Ile858ValVal 在线阅读现型变异性的变化.

更多相关视频

A Guide to Generating and Using hiPSC Derived NPCs for the Study of Neurological Diseases

A Guide to Generating and Using hiPSC Derived NPCs for the Study of Neurological Diseases

Published on: February 21, 2015

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

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,...