Approaches for developing peptide- and metal complexes- or chelators-based leads for anti-amyloid drugs

Abstract

Amyloids are abnormal protein aggregates that are associated with several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and prion diseases. The development of neurodrugs able to modulate amyloid aggregation represents a promising avenue for therapeutic intervention in neurodegenerative diseases. In recent years, peptides and metal complexes have emerged as attractive modulators of amyloid aggregation. Peptide-based approaches include the design of inhibitors of the amyloid self-assembly process or inhibitors of amyloid cross-interactions that may target specific regions of the amyloid protein crucial for aggregation. Interactions between metals and amyloidogenic proteins also play a significant role in the formation and stabilization of amyloid aggregates. Thus, metal complexes and metal chelators offer strategies to interfere with these metal-protein interactions and modulate amyloid aggregation. These complexes act by targeting the metal ions involved in amyloid aggregation, thereby disrupting their binding to amyloid peptides, inhibiting aggregation processes, and mitigating associated neurotoxicity. This comprehensive analysis emphasizes the considerable potential of peptides and metal complexes as effective modulators of amyloid aggregation, paving the way for the development of innovative peptide and metal-based neurodrugs with promising therapeutic applications in neurodegenerative disorders.