Neuroprotective and antioxidant capability of RW20 peptide from histone acetyltransferases caused by oxidative stress-induced neurotoxicity in in vivo zebrafish larval model

Oxidative stress causes disruption of cell macromolecules and resulting neurodegeneration when the antioxidant defense mechanism is inhibited. Oxidative stress is emerging as a key therapeutic target for nerve agent toxicity. Therefore, antioxidant treatment methods are a novel and effective approach to attenuate oxidative stress and neurodegeneration. This study evaluated the neuroprotective and antioxidant ability of a short peptide, RW20 derived from histone acetyltransferases (HATs). Using bioinformatics tools, the short amino acid sequence of RF13 peptide with antioxidant activity was predicted from HAT of Channa striatus transcriptome. The synthesized antioxidant peptide at various concentrations (10-50 mu M) was analyzed in in vitro and in vivo antioxidant assay. The neuroprotective effect of RF13 peptide was evaluated in H2O2 stressed zebrafish larvae. The results showed the neuroprotective effect by restoring antioxidant enzymes including SOD, CAT, GPx, GSH, and GST treated with RW20. In addition, the oxidative stress indicator of lipid peroxidation was gradually declined with an increase in the concentration of peptides. It was also shown to attenuate neuronal damage by inhibiting nitric oxide overproduction, thus increasing AChE activity. Further, to validate the neuroprotective effect of RW20, the intracellular ROS level and apoptosis in the zebrafish larvae were analyzed by incubating the larvae along with RW20, which decreased intracellular ROS level and reduced the cell death. Overall, the study demonstrated that RW20 possessed prominent antioxidant activity. Hence, we conclude that RW20 can be developed as a potent therapeutic agent against oxidative stress-induced neurodegenerative diseases. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study evaluated the neuroprotective and antioxidant ability of a short peptide, RW20, and demonstrated its prominent antioxidant activity. Therefore, RW20 may be developed as a potent therapeutic agent against oxidative stress-induced neurodegenerative diseases.