Astaxanthin Suppresses Amyloid-Beta-Induced Toxicity in AD Transgenic Caenorhabditis elegans via Promoting Skn-1-Dependent Proteasomal Activity.

Abstract

Astaxanthin is a ketocarotenoid that exhibits a variety of bioactivities, including neuroprotection, but the detailed mechanisms by which astaxanthin exerts neuroprotection remain unclear. In the present study, the effects of astaxanthin on amyloid-beta (Abeta)-induced toxicity were investigated in a Caenorhabditis elegans (C. elegans) model of Alzheimer's disease (AD). It is demonstrated that astaxanthin treatment significantly alleviated the Abeta-induced paralytic phenotype in AD C. elegans while reducing the production of reactive oxygen species and restoring the level of glutathione. Further analyses revealed that astaxanthin treatment resulted in a decrease in Abeta accumulation in AD C. elegans. Moreover, astaxanthin restored the proteasomal activity in AD C. elegans by elevating the expression of genes encoding the central subunits of the 20S proteasome. Therefore, astaxanthin might reduce Abeta accumulation via promoting proteasomal function. In addition, astaxanthin treatment increased the expression of skinhead-1 (skn-1), while knockdown of skn-1 expression by RNA interference diminished the inhibition of astaxanthin on Abeta-induced toxicity in AD C. elegans. The elevation of the expression of proteasome subunit genes and the enhancement of proteasomal activity by astaxanthin were also dependent on SKN-1. Overall, these findings indicated that astaxanthin exerted its protection against Abeta-induced toxicity in AD C. elegans via maintaining redox balance and promoting SKN-1-mediated proteasomal activity.