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

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Abstract

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.

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Acknowledgements

This research was funded by the Key-Area Research and Development Program of Guangdong Province (grant number 2020B020221002), the Guangdong Agricultural Science and Technology Innovation and Promotion Project of China (grant numbers 2020KJ142 & 2019KJ142) and the National Key Research and Development Program of China (grant number 2017YFC1701100). The authors thank AiMi Academic Services (www.aimieditor.com) for the English language editing and review services.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China

    Sichen Zhang, Chunguo Qian, Hailing Li, Zhimin Zhao & Depo Yang

  2. Guangdong Technology Research Center for Advanced Chinese Medicine, Guangzhou, China

    Sichen Zhang, Chunguo Qian, Hailing Li, Zhimin Zhao & Depo Yang

  3. Guangdong Museum of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China

    Jianchun Xian

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  1. Sichen Zhang
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Zhang, S., Qian, C., Li, H. et al. Structure–activity relationship of a housefly neuroprotective dodecapeptide that activates the nuclear factor erythroid 2-related factor 2 pathway. J Nat Med 77, 96–108 (2023). https://doi.org/10.1007/s11418-022-01650-1

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