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SORL1是tau的受体,促进了tau的播种

Joanna M Cooper¹, Aurelien Lathuiliere², Enming J Su³

¹The Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA.

The Journal of biological chemistry

|April 24, 2024

概括

索尔林相关受体1 (SORL1) 结合并内化,这是一个涉及阿尔茨海默病 (AD) 的蛋白质. 这种受体介导着的播种,可能将SORL1突变与AD病变发生联系起来.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

索尔林相关受体1 (SORL1) 是一种细胞内分类受体,与阿尔茨海默病 (AD) 有遗传联系.
SORL1影响了粉样蛋白前体蛋白 (APP) 贩运,这是AD的一个关键过程.
SORL1在TAU病理中的作用,这是AD的另一个标志,仍然在很大程度上未被探索.

研究的目的:

为了研究SORL1和tau蛋白之间的直接结合相互作用.
为了确定SORL1是否调节细胞吸收和贩运.
评估SORL1在调节聚和播种中的作用,特别是在AD的背景下.

主要方法:

使用表面等离子体共振 (SPR) 来量化tau与SORL1.1的结合亲和力.
使用免疫光显微镜可视化神经瘤细胞中tau和SORL1的同位化.
在细胞模型中使用了SORL1的过度表达和siRNA淘汰,以评估其在内部化和播种中的作用.
使用FRET生物传感器细胞监测野生类型和突变SORL1.1.存在的tau播种.

主要成果:

在生理和内体的pH值下,SORL1对tau表现出高亲和度的结合.
SORL1促进单体的内部化进入细胞.
SORL1的表达增强了tau的播种,特别是来自AD患者大脑的tau.
一种特定的SORL1突变 (N1358S) 显著增加了种植,这表明与AD有直接联系.

结论:

SORL1作为的直接受体,调解其细胞吸收和贩运.
在病原性聚物播种中,SORL1起着至关重要的作用.
这些发现确定了一种新的机制,通过tau病理学将SORL1功能障碍和突变与阿尔茨海默病的发病因子联系起来.

关键词:

这就是SORL1的原因.阿波利波蛋白E (ApoE) 是一种脂蛋白受体相关蛋白 (LRP) 是一种与脂蛋白受体相关的蛋白质.神经退行性疾病是一种神经退行性疾病.蛋白 (tau) 是一种蛋白.塔乌播种的种子病症是一种病症.

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