神经退行性变
秀丽隐杆线虫
信号转导
胰岛素受体
胰岛素
转录因子
内分泌学
胰岛素样生长因子
内科学
阿尔茨海默病
疾病
神经科学
细胞生物学
医学
生物
遗传学
生长因子
胰岛素抵抗
受体
基因
作者
Yi Xiao,Yan Zhang,Linlu Li,Nian Jiang,Changyan Yu,Sanhua Li,Xinting Zhu,Fang Liu,Yun Liu
标识
DOI:10.1016/j.archger.2024.105377
摘要
The evolutionarily conserved insulin/IGF-1 signaling pathway plays a central role in aging and aging related diseases such as neurodegeneration diseases. Inhibition of insulin/IGF-1 signaling pathway has been proposed as a effective way to extend lifespan and delay neurodegeneration diseases in different organisms. Cynaroside (Cyn), a flavonoid contained in many medical plants and in vegetables, had been shown to exhibit pharmacological properties such as anti-inflammatory, anti-tumor, and anti-oxidant effects. The study demonstrated that lifespan extension and neurodegeneration diseases improving could be achieved by targeting evolutionarily conserved insulin/IGF-1 pathway through using pharmacological interventions. Via using this approach in tractable model Caenorhabditis elegans, We found that 10 μM Cynaroside significantly promoted the healthy lifespan in wild-type animals. Furthermore, via genetic screen, we showed that Cynaroside acted on IGF-1-R /DAF-2, which was followed by the activation of transcription factor DAF-16/FOXO to extend the healthy lifespan. Intriguingly, Cynaroside also improved neurodegeneration diseases such as Alzheimer's and polyglutamine disease by suppressing insulin/IGF-1 signaling pathway. Our work suggests that Cynaroside may be a promising candidate for the prevention and treatment of aging and neurodegeneration diseases.
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