隐丹参酮通过缓解氧化应激和降低异常聚集蛋白水平在C. elegans AD模型中发挥神经保护作用

Abstract

Alzheimer’s disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated fromSalvia castanea. It is found that it can alleviate AD-like features associated with Aβ1-42toxicity in muscle cells as well as neuronal cells ofCaenorhabditis elegans(C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression ofsod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aβ monomers and highly toxic oligomers inC. eleganswhile inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression ofhsp-16.2and downregulated the expression oface-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.Keywords:Alzheimer’s disease;cryptotanshinone;Caenorhabditis elegans;Aβ;oxidative stress