Food-derived bioactive peptides with neuroprotective properties: a narrative review

Neuroprotective peptides, a class of bioactive peptides naturally derived from food sources, exhibit strong potential in neuroprotection and the promotion of neural development. These peptides are characterized by high bioavailability, favorable safety profiles, and multifunctional physiological benefits. Notably, specific peptides such as PW5 (Pro-Trp-Trp-Trp-Trp-Trp) and WHP (Trp-His-Pro) have demonstrated significant efficacy in reducing oxidative stress, inhibiting neuroinflammation, and attenuating neuronal apoptosis in both in vitro and in vivo models of cognitive impairment. These actions are comparable to neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), contributing to improved synaptic plasticity and enhanced cognitive function. Clinically, these peptides offer promising adjunct or alternative strategies for managing neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), especially in early-stage interventions or dietary-based therapies. This review summarizes recent advances in food-derived neuroprotective peptides, with particular emphasis on their neuroprotective mechanisms, bioavailability challenges, BBB transport, and delivery approaches. It further highlights current research gaps and provides perspectives for future investigations aimed at facilitating the rational development and potential application of these peptides. Current research faces key limitations, including the incomplete understanding of structure-activity relationships, insufficient evidence regarding blood-brain barrier (BBB) permeability, limited knowledge of peptide stability in complex biological environments, and the lack of comprehensive long-term safety evaluations. Future studies should prioritize systematic peptide screening, mechanism-oriented structure optimization, and advanced delivery strategies to improve the bioavailability and functional efficacy of food-derived neuroprotective peptides.