Self-assembled metabolite-derived amyloid-like structures: implications for disease, therapeutics, and biomedical applications.

Metabolites are fundamental components that regulate a wide range of biological processes in living organisms. This review focuses on recent advancements in amyloid metabolites, particularly their formation through processes such as self-assembly, propagation, interaction, and transmission. Further we have highlighted amyloid metabolites in metabolic disorders and neurodegenerative diseases. Our findings, alongside those of others in the field, reveal that metabolite assemblies significantly extend the traditional amyloid formation hypothesis. Furthermore, the self-assembly pathways of metabolites determine the shape, size, internal structure, and dimensions of the resulting nanostructures, influencing their biological activity. This growing body of work offers novel insights into the pathophysiology of inborn errors of metabolism (IEMs) and links them to amyloid-related diseases, which are typically characterized by protein and polypeptide aggregation. Additionally, we discuss the role of metabolites in forming stable, functional self-assemblies across various organisms. These assemblies show great promise for biomedical applications, as they present high densities of biological signals on their surfaces, enabling targeted interactions, pathway activation, and enhanced biocompatibility and biodegradability. Finally, this review provides an updated understanding of the assembly behaviours, biological functions, and potential applications of amyloid metabolites.