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

作者：Fanrui Zhao, Chunlei Liu, Li Fang, Hongyan Lu, Ji Wang, Yawen Gao, Rosita Gabbianelli, Weihong Min · 发表于：Journal of Agricultural and Food Chemistry · 年份：2021 · DOI：10.1021/acs.jafc.0c07546 · 被引用次数：75 · 研究领域：Autophagy in Disease and Therapy、Genomics, phytochemicals, and oxidative stress、Mitochondrial Function and Pathology

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 H 2 O 2 -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 H 2 O 2 -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.