Walnut-Derived Peptide Activates PINK1 via the NRF2/KEAP1/HO-1 Pathway, Promotes Mitophagy, and Alleviates Learning and Memory Impairments in a Mice Model,Journal of Agricultural and Food Chemistry

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Walnut-Derived Peptide Activates PINK1 via the NRF2/KEAP1/HO-1 Pathway, Promotes Mitophagy, and Alleviates Learning and Memory Impairments in a Mice Model
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-02-16 , DOI: 10.1021/acs.jafc.0c07546
Fanrui Zhao _{1,

2,

3} , Chunlei Liu _{1,

2} , Li Fang _{1,

2} , Hongyan Lu _{1,

2} , Ji Wang _{1,

2} , Yawen Gao _{1,

2} , Rosita Gabbianelli ₄ , Weihong Min _{1,

2}

Affiliation

Mitophagy has a pivotal protective function in the pathogenesis of neurological disorders. However, the mechanism of its modulation remains elusive, especially in PINK1-mediated mitophagy. Here, we investigated the neuroprotective effects of a walnut-derived peptide, YVLLPSPK, against scopolamine-induced cognitive deficits in mice and explored the underlying PINK1-mediated mitophagy mechanisms in H₂O₂-treated HT-22 cells. Using the Morris water maze, we showed that YVLLPSPK relieved the cognitive deficiency by alleviating oxidative stress. Mitochondrial morphology was observed in mice hippocampal tissues using transmission electron microscopy (TEM). Both Western blot and immunofluorescence analysis illustrated YVLLPSPK promoted the expression of mitophagy-related proteins and activated the NRF2/KEAP1/HO-1 pathway. Subsequently, an NRF2 inhibitor (ML385) was used to verify the contribution of the YVLLPSPK-regulated NRF2/KEAP1/HO-1 pathway in PINK1-mediated mitophagy in H₂O₂-treated HT-22 cells. These data suggested that YVLLPSPK improved learning and memory in scopolamine-induced cognitive-impaired mice through a mechanism associated with PINK1-mediated mitophagy via the NRF2/KEAP1/HO-1 pathway.

中文翻译：

核桃衍生肽通过 NRF2/KEAP1/HO-1 通路激活 PINK1，促进线粒体自噬，并减轻小鼠模型中的学习和记忆障碍

线粒体自噬在神经系统疾病的发病机制中具有关键的保护作用。然而，其调节机制仍然难以捉摸，尤其是在 PINK1 介导的线粒体自噬中。在这里，我们研究了核桃衍生肽 YVLLPSPK 对东莨菪碱诱导的小鼠认知缺陷的神经保护作用，并探索了 H ₂ O _{2中潜在的 PINK1 介导的线粒体自噬机制}-处理的 HT-22 细胞。使用莫里斯水迷宫，我们发现 YVLLPSPK 通过减轻氧化应激来缓解认知缺陷。使用透射电子显微镜（TEM）在小鼠海马组织中观察线粒体形态。Western印迹和免疫荧光分析均表明YVLLPSPK促进线粒体自噬相关蛋白的表达并激活NRF2/KEAP1/HO-1通路。随后，使用 NRF2 抑制剂 (ML385) 验证 YVLLPSPK 调节的 NRF2/KEAP1/HO-1 通路在 PINK1 介导的 H ₂ O _{2线粒体自噬中的作用}-处理的 HT-22 细胞。这些数据表明，YVLLPSPK 通过与 PINK1 介导的 NRF2/KEAP1/HO-1 通路的线粒体自噬相关的机制，改善了东莨菪碱诱导的认知受损小鼠的学习和记忆。

更新日期：2021-03-10

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