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SKN-1 is indispensable for protection against Aβ-induced proteotoxicity by a selenopeptide derived from Cordyceps
Mengfei Chen1, Zhenjun Zhu2, Shujian Wu2
1Department of Food Science and Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China; Institute of Microbiology, Guangdong Academy of Sciences, State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Safety and Health, National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Guangzhou, 510070, China.
Abstract:
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.
Insights
The selenopeptide VPRKL(Se)M reduces amyloid-beta toxicity by inhibiting protein aggregates and oxidative stress. This protective effect in C. elegans depends on the SKN-1 pathway, suggesting therapeutic potential for protein-disorder diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Oxidative stress and proteostasis disruption drive cell death in diseases.
- Selenopeptides show potential for managing oxidative stress and inflammation.
- The role of selenopeptides in inhibiting proteotoxicity remains unclear.
Purpose of the Study:
- Investigate VPRKL(Se)M's effects on amyloid-beta (Aβ) toxicity.
- Elucidate the mechanisms underlying VPRKL(Se)M's action in a C. elegans model.
Main Methods:
- Utilized transgenic Caenorhabditis elegans expressing amyloid-beta.
- Administered VPRKL(Se)M to assess its impact on Aβ toxicity.
- Measured reactive oxygen species (ROS) levels and proteostasis markers.
- Investigated the role of the SKN-1 pathway.
Main Results:
- VPRKL(Se)M supplementation alleviated Aβ-induced toxicity in C. elegans.
- VPRKL(Se)M inhibited Aβ aggregate formation and reduced ROS levels.
- Proteostasis was improved by VPRKL(Se)M treatment.
- The protective effects were dependent on the skinhead-1 (SKN-1) pathway.
Conclusions:
- VPRKL(Se)M demonstrates potential as a therapeutic agent against Aβ toxicity.
- The mechanism involves modulating SKN-1 to enhance proteostasis and reduce oxidative stress.
- VPRKL(Se)M may be crucial in preventing protein-disorder related diseases.
