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

Abstract

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 PINK1mediated 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 scopolamineinduced cognitive-impaired mice through a mechanism associated with PINK1-mediated mitophagy via the NRF2/KEAP1/HO-1 pathway.

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury

“…Interestingly, Bertrand and colleagues found that the synthetic Nrf2 activator, 1,4-diphenyl-1,2,3-triazole compound, promotes mitophagy and plays a contributory role in regulating mitochondrial homeostasis [ 43 ]. Current studies have found that some potential antioxidants such as walnut-derived peptide and MitoQ can facilitate PINK1/Parkin-mediated mitophagy and obstruct OS by activating the Nrf2 signaling pathway [ 17 , 18 ]. However, the potential targets of maltol on mitochondrial functions have not been well studied.…”

“…Accumulating research suggests that some chemical antioxidants such as walnut-derived peptide and MitoQ can enhance mitophagy by obstructing OS and apoptosis via facilitating the Nrf2/PINK1/Parkin signaling pathway [ 17 , 18 ]. However, maltol (3-hydroxy-2-methyl-4-pyrone, C 6 H 6 O 3 ) is a Maillard reaction product by the pyrolysis of starch or sucrose and is widely applied as a reliable food additive and a natural antioxidative agent [ 19 ].…”

Characteristics and Antioxidant Activity of Walnut Oil Using Various Pretreatment and Processing Technologies

“…Chinese walnut production is 1.78 million tons and its output is 4795.9 kilotons, which accounts for half of the world’s walnut production (2020, FAO stat). Walnuts have been eaten in China for thousands of years, influenced by the traditional concept of “shape compensation”, as the kinds of nuts that have benefits for brain health [ 2 ]. This speculation has also been demonstrated in walnut oil; a recent date showed that walnut oil could reduce memory impairment in mice [ 3 ] because walnut oil has anti-inflammatory properties [ 4 ].…”

Protective effects of curcumin/cyclodextrin polymer inclusion complex against hydrogen peroxide‐induced LO2 cells damage

“…As an important component of ROS, H 2 O 2 is generated under various physiological or pathological conditions and leads to oxidative injury (Li et al., 2012 ). H 2 O 2 is a common inducer to induce oxidative stress in vitro models of oxidative damage (Chen et al., 2021 ; Zhao et al., 2021 ). Besides, in the study of liver injury, LO2 cell line has been commonly used (Hu et al., 2015 ; Wang et al., 2008 ).…”