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神经红素-MYH9相互作用调节脑血管结构中的细胞骨重塑

Adesewa Akande¹, Ji Eun Park¹, Rona Scott²

¹Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA.

Fluids and barriers of the CNS

|October 1, 2025

概括

神经红素 (Ng) 通过MYH9调节大脑内皮细胞细胞骨重塑,保持血脑屏障的完整性. 这种新发现的ng功能对大脑健康至关重要,可能会影响阿尔茨海默病.

科学领域:

神经科学是一个神经科学.
细胞生物学细胞生物学
生物化学生物化学

背景情况:

神经红素 (Ng) 是一种已知的神经元--卡尔莫杜林信号的调节剂,与阿尔茨海默病有关.
在大脑血管系统,特别是内皮细胞中的NG的功能基本上是未知的.
了解NG在大脑微血管系统中的作用对于了解大脑健康和疾病至关重要.

研究的目的:

为了研究神经红素 (Ng) 在大脑微血管内皮细胞中的功能.
为了识别NG结合蛋白,并阐明NG在大脑血管系统中的分子相互作用.
探索NG在维持血脑屏障完整性方面的潜在作用.

主要方法:

免疫沉质谱 (IP-MS) 用于在不同的条件下定义Ng相互作用体.
通过使用CaM亲和力拉低和近距离结合试验验证Ng-MYH9相互作用的验证.
评估F-actin水平,AKT-GSK3β信号传递,VCAM1表达和脑微血管架构在Ng或MYH9敲除后以及在Ng-null小鼠中.

主要成果:

鉴定了119个结合蛋白,包括与MYH9的新型相互作用,一个细胞骨调节器,在高下突出.
Ng knockdown降低了F-actin,而MYH9 knockdown影响了Ng和F-actin的水平.
Ng-MYH9相互作用的丧失损害了AKT-GSK3β信号传递,增加了内皮激活 (VCAM1),破坏了微血管结构,并减少了内皮细胞中的MYH9表达.

结论:

神经红素 (Ng) 与MYH9相互作用,促进大脑内皮细胞中MYH9依赖的细胞骨重塑.
在维持血脑屏障完整性方面发挥了以前未知的作用.
这种新的Ng路径对大脑健康有意义,可能与阿尔茨海默病的发病相关.

关键词:

细胞骨重塑细胞骨重塑免疫沉质谱法质谱学互动组是互动组的组成部分.肌酸氨酸-9是什么意思神经激素素是一种神经激素.

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