Amyloids. Evolutionary Past and Biotechnological Future

It is widely known that, in higher eukaryotes, the amyloid form of a number of proteins that control neuronal activity leads to the shutdown of their function and toxicity, which causes severe neurodegenerative diseases. However, over the past decade, evidence has accumulated that the amyloid state may be beneficial to the cell and play an important role in protein metabolism. It is believed that the ability to form an amyloid structure is largely determined by certain short sequences, among which the most studied are prion domains. In addition to highly hydrophobic regions that are prone to forming a β-sheet secondary structure, they also include small segments of intrinsically disordered regions, called cryptic amyloidogenic regions (CARs), through which interactions with other biomolecules occur. It is suggested that CARs played an important role in protein evolution: CAR-like sequences could be converted into interactive regions that form homotypic and heterotypic contacts and thus contribute to the formation of the first oligomeric complexes and coacervates. It has been shown that proteins belonging to the most ancient living organisms, such as bacteria and archaea containing prion domains. This suggests that prionlike proteins preceded other protein forms. It is believed that they may have been one of the first molecules of the prebiotic world due to their ability to self-assemble and self-reproduce. In addition, it has now been proven that amyloidization of proteins is not limited to switching off their function, but can contribute to adaptation in a wide range of organisms. For example, amyloids can act as stimulants, catalyzing a variety of reactions (most often hydrolysis). It is hypothesized that they gave rise to biocatalysis and determined the further paths of enzyme evolution. Based on functional amyloids, a new direction of biotechnology has now emerged, which is associated with biomaterials for use in various areas of light industry, as well as, most importantly, in pharmacology and medicine, where, thanks to it, new opportunities for tissue therapy and stem-cell therapy are being realized.