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一个多层网络模型将Akt1确定为神经退行症的常见调节器

Dokyun Na¹, Do-Hwan Lim^2,3, Jae-Sang Hong^2,4

¹Department of Biomedical Engineering, Chung-Ang University, Seoul, Republic of Korea.

Molecular systems biology

|November 20, 2023

概括

一个新的网络模型 (MLnet) 确定了神经退行性疾病 (ND) 中常见的蛋白质修饰剂,如胰岛素通路. 激活Akt1与SC79的信号传递,提高了阿尔茨海默氏症患者的细胞活力和增强记忆力.

科学领域:

神经科学是一个神经科学.
计算生物学计算生物学
遗传学遗传学是一个

背景情况:

神经退行性疾病 (NDs) 分享蛋白质错折和聚合.
多个NDs共同的潜在分子机制尚未得到充分理解.
确定共享的途径可以揭示更广泛的治疗目标.

研究的目的:

开发一个计算模型 (MLnet) 来预测跨疾病群体的常见蛋白质修饰剂.
为多种神经退行性疾病确定具有病理生理学相关性的分子通路.
为了验证预测的目标,并探索他们的治疗潜力.

主要方法:

开发了一个多层网络扩展 (MLnet) 模型.
应用MLnet来预测阿尔茨海默氏症,亨廷顿氏症和两个脊髓小脑动症的常见修饰剂.
使用Drosophila和基于人类细胞的神经退行性疾病模型的验证预测.
在细胞和小鼠模型中使用小分子SC79测试了Akt1激活的治疗潜力.

主要成果:

MLnet预测了关键的胰岛素通路成员 (PDK1,Akt1,InR,GSK-3β) 作为常见的修饰剂.
在多个ND模型中,激活与SC79信号的Akt1增加了细胞活力.
在阿尔茨海默氏症模型小鼠中,SC79治疗改善了长期记忆和焦虑行为.

结论:

MLnet是发现疾病群体中共享的分子通路的宝贵工具.
胰岛素通路,特别是Akt1,是多种神经退行性疾病的潜在治疗点.
准Akt1信号显示出治疗神经退行性疾病的前景.

关键词:

一个常见的修改器修改器.胰岛素的信号通路.多层网络扩展的多层网络扩展.神经退行性疾病的神经退行性疾病蛋白质稳定症是一种蛋白质稳定症.

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