Peptide-based inhibitors and nanoparticles: Emerging therapeutics for Alzheimer's disease

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and behavioral changes, impacting millions of individuals worldwide. Despite significant research into its cellular and molecular mechanisms, no cure has been found to treat AD to date. For over two decades, research aimed at treating AD has focused on targeting amyloid-β (Aβ); however, these strategies have not demonstrated substantial effectiveness. Consequently, research is now expanding towards targeting other hallmarks of the disease, such as tau protein and brain metal ions. Among potential therapeutics against these pathophysiological targets, peptide-based inhibitors are notable for their high selectivity and low toxicity. Despite these advantages, they face obstacles such as a short half-life in vivo and low efficiencies in crossing the blood-brain barrier (BBB). The use of nanoparticles (NPs) to deliver peptide-based inhibitors to the brain offers unique advantages, such as enhanced stability against degradation, improvement in targeted delivery, and reduced potential for immunogenic responses. This review aims to provide a comprehensive overview of emerging peptides tested as treatments for AD against Aβ, tau protein, and brain metal ions and to evaluate NPs as a means to overcome the limitations. These peptide-based inhibitors are promising, as they not only alleviate symptoms but also aim to prevent progressive neuronal loss, and NPs can be highly effective in delivering these inhibitors.