Peptide and Peptidomimetic Strategies to Probe and Modulate Neurodegenerative Mechanisms

Bioactive peptides and peptidomimetics play fundamental roles in biological signaling and have long demonstrated utility as molecular tools and therapeutic candidates. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—aberrant protein folding, aggregation, and peptide–protein interactions contribute directly to neuronal dysfunction, neuroinflammation, and progressive degeneration. Metal ions such as copper, zinc, and iron are closely bound up with these processes, influencing peptide conformation, aggregation propensity, and oxidative injury in vulnerable neuronal populations. Targeting these molecular processes using peptide-based strategies offers a powerful approach for dissecting disease mechanisms, identifying biomarkers, and validating novel therapeutic targets.This Research Topic focuses on mechanistic and preclinical investigations of peptide- and peptidomimetic-based approaches that modulate pathogenic protein interactions, metal–peptide and metal–protein interactions, neuroinflammatory pathways, and neuronal vulnerability in neurodegenerative disease models. Emphasis is placed on studies that clarify cellular and molecular mechanisms, define pathway-specific effects, and advance understanding of how peptide-based tools influence disease-relevant processes.We particularly welcome contributions that integrate biochemical, cellular, and in vivo approaches to interrogate protein–protein, protein–peptide, and neuron–peptide interactions in established models of neurodegenerative disease. Studies employing animal models or other preclinical systems to validate mechanisms of action and identify disease-relevant molecular signatures are strongly encouraged.This Research Topic aims to provide a mechanistically grounded and integrative overview of peptide and peptidomimetic strategies that advance understanding of neurodegenerative disease biology, rather than purely descriptive or outcome-focused therapeutic reports.We welcome Original Research, Reviews, and Perspectives covering, but not limited to:- Mechanistic studies of protein–protein and protein–peptide interactions relevant to neurodegenerative pathology- Peptide-based modulation of protein aggregation, misfolding, or clearance pathways- Metal-binding peptides and peptidomimetics as tools to probe or modulate protein aggregation, misfolding, and clearance in neurodegenerative disease models- Disruption of metallostasis in neurodegeneration: mechanistic studies of copper, zinc, and iron handling in disease-relevant cellular and in vivo systems- Cellular and molecular mechanisms underlying peptide-mediated regulation of neuroinflammation in neurodegeneration- Preclinical and in vivo studies evaluating peptide or protein vaccines and adjuvants with defined mechanisms of action- Peptide-functionalized nanoparticles or extracellular vesicles as tools for probing or modulating neurodegenerative pathways- Peptidomimetic strategies for target validation, biomarker discovery, or pathway dissection in neurodegenerative disease models- Peptide-functionalized nanoparticles in neuron–glia dialogueStudies primarily focused on clinical outcomes, generalized neuroprotection, non-degenerative inflammatory models, or purely chemical characterisation of metal complexes without demonstrated relevance to neurodegenerative mechanisms are considered outside the scope of this Research Topic. Topic editors: Nabanita Mukherjee, Marta Sidoryk-Wegrzynowicz, Claudio Villegas-Llerena, Enrico Rizzarelli, ANAHI CHAVARRIA Source: https://www.frontiersin.org/research-topics/80614/peptide-and-peptidomimetic-strategies-to-probe-and-modulate-neurodegenerative-mechanisms