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.

神经保护性抗氧化剂，尤其是基于肽的抗氧化剂，可有效对抗神经退行性疾病中的氧化应激。在这项研究中，我们测量了来自家蝇Musca domestica的抗氧化肽 DFTPPVCTTELGR (DR12) 的神经保护作用L. 蛹。用 DR12 处理 PC12 和 HT22 细胞可显着降低谷氨酸诱导的细胞毒性。肽 DR12 似乎通过减少活性氧和丙二醛的产生、上调内源性抗氧化剂超氧化物歧化酶和谷胱甘肽以及逆转线粒体膜电位的丧失来发挥其神经保护作用。此外，DR12 治疗激活了核因子红细胞 2 相关因子 2/血红素加氧酶 1 信号通路。构效分析表明 DR12 的优越神经保护功能与其半胱氨酸残基有关。总之，DR12 可能是一种有吸引力的治疗性肽或治疗神经退行性疾病的前体。