Modulation of neuropathological pathways by bioactive peptides and proteins/polypeptides: Targeting oxidative stress in neurodegenerative diseases

Abstract

Neurodegenerative disorders (NDDs) pose a growing global health burden, primarily due to their progressive nature and the limited efficacy of existing treatments. Bioactive peptides and proteins/polypeptides, particularly those derived from dietary and natural sources, show promise in modulating neurobiological pathways central to neurodegeneration. This review aims to critically examine the neuroprotective roles of Bioactive peptides and proteins/polypeptides in NDDs, elucidating their mechanisms of action, potential therapeutic applications in conditions like Alzheimer's, Parkinso's disease, Huntington's disease, and others, as well as the trends in peptide-based therapeutics. Bioactive peptides and proteins/polyspeptides, such as NGF, BDNF, GDNF, Semax, and Exendin-4, have been found to modulate several critical mechanisms, including the reduction of oxidative stress (OS), inhibition of neuroinflammation, preservation of mitochondria, and enhancement of synaptic plasticity. These peptides have demonstrated efficacy in preclinical and early-phase clinical trials across a spectrum of NDDs. Delivery challenges, such as blood-brain barrier (BBB) permeability and enzymatic degradation, have been acknowledged. Ongoing innovations in peptide engineering, nanoparticle-based delivery systems, CRISPR-assisted design, and AI-driven screening are addressing these limitations. By targeting multiple pathogenic mechanisms simultaneously, peptide-based therapeutics present a rational and innovative approach to NDD management. Their multifunctional action profiles and ability to target specific molecular pathways highlight their potential as next-generation neuroprotective agents. However, future clinical validation and advanced strategies are essential for translating these promising molecules into effective treatments.