Experimental results proved that MWHP exhibits potential in improving memory and should be used to develop novel functional food. © 2018 Society of Chemical Industry.

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.

A novel neuroprotective peptide EVSGPGLSPN, which was identified from walnut protein hydrolysates, protected PC12 cells by blocking the NF-κB/caspase pathways.

Natural-derived peptides are effective substances in attenuating oxidative stress. However, their specific mechanisms have not been fully elucidated, especially in peptide-mediated autophagy. In the present study, TWLPLPR, YVLLPSPK, and KVPPLLY, novel peptides from Juglans mandshurica Maxim, prevented reactive oxygen species (ROS) production, elevated glutathione peroxidase (GSH-Px) activity and adenosine 5′-triphosphate (ATP) levels, and ameliorated apoptosis in Aβ25–35 (at a concentration of 50 μM for 24 h)-induced PC12 cells (P < 0.01). Both western blot and immunofluorescence analysis illustrated that the peptides regulated Akt/mTOR signaling through p-Akt (Ser473) and p-mTOR (S2481) and promoted autophagy by increasing the levels of LC3-II/LC3-I and Beclin-1 while lowering p62 expression (P < 0.01). The autophagy inhibitor (3-methyladenine, 3-MA) and inducer (rapamycin, RAPA) were combined used to confirm the contribution of peptide-regulated autophagy in antioxidative effects. Moreover, the peptides increased the levels of LAMP1, LAMP2, and Cathepsin D (P < 0.05) and promoted the fusion with lysosomes to form autolysosomes, accelerating ROS removal. These data suggested that walnut-derived peptides regulated oxidative stress by promoting autophagy in the Aβ25–35-induced PC12 cells.

This study aimed to investigate the effects of a pine nut albumin hydrolysate (fraction < 3 kDa) and of its short peptide derivative, Trp-Tyr-Pro-Gly-Lys (WYPGK), on synaptic plasticity and memory...