Metabolite assemblies: A surprising extension to the amyloid hypothesis

The realization of the ability of metabolites to form self-assembled amyloid-like nanostructures was a surprising phe-nomenon. This discovery paved the way towards understanding the pathophysiology of the inborn error of metabolism disorders from a new perspective, relating them to amyloid-associated diseases that are characterized by the aggregation of proteins and polypeptides. Hence, a 'generic amyloid hypothesis' can be proposed. This theory implies that the formation of amyloid-like structures is a general phenomenon not limited to proteins and reflects a common etiology for both age-related amyloid-associated diseases and inborn error of metabolism disorders. Here, we present a comprehensive survey of the recent research related to metabolite amyloids including their structure formation through self-association, propagation, interactions, trans-mission, and their role in metabolic disorders and neurodegen-erative diseases and their applications for the fabrication of novel materials which implicate metabolite assemblies as a surprising extension to the amyloid scheme.