Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, represent an increasing global public health challenge, driven by population aging and the lack of effective curative therapies. In this context, plant-derived peptides have emerged as promising bioactive compounds due to their multitarget neuroprotective properties and favorable safety profiles. This review provides a comprehensive overview of plant peptides with reported activity against neurodegeneration, highlighting their natural sources, biological activities, and mechanisms of action. Evidence from in vitro and in vivo models indicates that these peptides act through multiple complementary pathways, including attenuation of oxidative stress, modulation of neuroinflammation, regulation of apoptosis, preservation of mitochondrial function, and inhibition of toxic protein aggregation. Additionally, several peptides have been shown to enhance synaptic plasticity, modulate neurotransmission, and regulate ion channel activity, suggesting beneficial effects on neuronal communication and cognitive function. Some studies explored structural modifications, such as the introduction of specific residues or glycosylation, which have resulted in greater stability and enhanced efficacy against oxidative insults. Overall, plant-derived peptides demonstrate consistent neuroprotective effects and low toxicity; however, challenges related to the blood–brain barrier, bioavailability, and the understanding of molecular mechanisms must still be overcome to enable their clinical application.
Maia et al. (2026) studied this question.