SKN-1 is indispensable for protection against Aβ-induced proteotoxicity by a selenopeptide derived from Cordyceps militaris

• Published in: Redox biology 2024-04, Vol.70, p.103065, Article 103065
• Main Authors: Chen, Mengfei, Zhu, Zhenjun, Wu, Shujian, Huang, Aohuan, Xie, Zhiqing, Cai, Jie, Huang, Rong, Yu, Shubo, Liu, Ming, Zhang, Jumei, Tse, Yuchung, Wu, Qingping, Wang, Juan, Ding, Yu
• Format: Article
• Language: English
• Subjects: Aβ-induced toxicity; Caenorhabditis elegans; Proteostasis; Selenopeptides; SKN-1
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2024.103065

Oxidative stress (OS) and disruption of proteostasis caused by aggregated proteins are the primary causes of cell death in various diseases. Selenopeptides have shown the potential to control OS and alleviate inflammatory damage, suggesting promising therapeutic applications. However, their potential function in inhibiting proteotoxicity is not yet fully understood. To address this gap in knowledge, this study aimed to investigate the effects and underlying mechanisms of the selenopeptide VPRKL(Se)M on amyloid β protein (Aβ) toxicity in transgenic Caenorhabditis elegans. The results revealed that supplementation with VPRKL(Se)M can alleviate Aβ-induced toxic effects in the transgenic C. elegans model. Moreover, the addition of VPRKL(Se)M inhibited the Aβ aggregates formation, reduced the reactive oxygen species (ROS) levels, and ameliorated the overall proteostasis. Importantly, we found that the inhibitory effects of VPRKL(Se)M on Aβ toxicity and activation of the unfolded protein are dependent on skinhead-1 (SKN-1). These findings suggested that VPRKL(Se)M is a potential bioactive agent for modulating SKN-1, which subsequently improves proteostasis and reduces OS. Collectively, the findings from the current study suggests VPRKL(Se)M may play a critical role in preventing protein disorder and related diseases. [Display omitted] •VPRKL(Se)M confers protection against Aβ-induced proteotoxicity.•The activation of UPR by VPRKL(Se)M needs SKN-1.•SKN-1 is indispensable for VPRKL(Se)M to protect against Aβ-induced proteotoxicity.