Structure–activity relationship of a housefly neuroprotective dodecapeptide that activates the nuclear factor erythroid 2-related factor 2 pathway

• Published in: Journal of natural medicines Vol. 77; no. 1; pp. 96 - 108
• Main Authors: Zhang, Sichen, Qian, Chunguo, Li, Hailing, Zhao, Zhimin, Xian, Jianchun, Yang, Depo
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 2023; Springer Nature B.V
• Subjects: Animals; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Biomedical and Life Sciences; Biomedicine; Complementary & Alternative Medicine; Cytotoxicity; Glutathione; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - metabolism; Houseflies - metabolism; Malondialdehyde; Medicinal Chemistry; Membrane potential; Mitochondria; Neurodegenerative diseases; Neuroprotection; Neuroprotective Agents - pharmacology; NF-E2-Related Factor 2 - metabolism; Original Paper; Oxidative Stress; Oxygenase; Peptides; Peptides - pharmacology; Pharmacology/Toxicology; Pharmacy; Plant Sciences; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal transduction; Structure-Activity Relationship; Superoxide dismutase; Structure–activity; Neuroprotection; Oxidative stress; Antioxidant peptide; Nuclear factor erythroid 2-related factor 2
• ISSN: 1340-3443; 1861-0293
• DOI: 10.1007/s11418-022-01650-1

Neuroprotective antioxidants, especially peptide-based antioxidants, are effective against oxidative stress in neurodegenerative disorders. In this study, we measured the neuroprotective effects of the antioxidant peptide DFTPVCTTELGR (DR12) from housefly Musca domestica L. pupae. Treatment of PC12 and HT22 cells with DR12 significantly reduced glutamate-induced cytotoxicity. Peptide DR12 appeared to exert its neuroprotective effects by attenuating production of reactive oxygen species and malonaldehyde, upregulating the endogenous antioxidants superoxide dismutase and glutathione, and reversing the loss of mitochondrial membrane potential. In addition, DR12 treatment activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Structure–activity analysis indicated that the superior neuroprotective function of DR12 was related to its cysteine residue. In summary, DR12 may be an attractive therapeutic peptide or precursor to treat neurodegenerative diseases.