Transcriptomic response of Caenorhabditis elegans expressing human Aβ42 gene treated with Salvianolic acid A

Abstract

AbstractAlzheimer’s disease (AD) is a brain disease attributed to the accumulation of extracellular senile plaques comprising β-amyloid peptide (Aβ). In this study, a global transcriptomic analysis of the response of transgenic Caenorhabditis elegans worms expressing full length human Aβ42 gene towards Salvianolic acid A (Sal A) was analysed. Antioxidant response genes, namely gst-4, gst-10, spr-1 and trxr-2, were upregulated. The production of Aβ42 caused oxidative stress and the antioxidant response genes possibly provide defence to the strain. The gene product of trxr-2 also functionally interacts with the defence system and has a role in life span. Genes involved in replication, reproduction, immune response to microbes and antimicrobial activities were also upregulated. Exposure to Sal A also increased the rate of reproduction of nematodes, and heightened its immunological protection system towards microorganisms. In contrast, genes responsible for locomotion, ligand-gated cation channel, embryonic and postembryonic development, and neuromodulation of chemosensory neurons were significantly down-regulated. As an effector, Sal A might conceivably reduce the movement of the worm by interfering with neuronal transmission and embryonic and post-embryonic development.