Functional Mammalian Amyloids and Amyloid-Like Proteins

Abstract

Amyloids are highly ordered fibrous cross-β protein aggregates that are notorious primarily because of association with a variety of incurable human and animal diseases (termed amyloidoses), including Alzheimer’s disease (AD), Parkinson’s disease (PD), type 2 diabetes (T2D), and prion diseases. Some amyloid-associated diseases, in particular T2D and AD, are widespread and affect hundreds of millions of people all over the world. However, recently it has become evident that many amyloids, termed “functional amyloids,” are involved in various activities that are beneficial to organisms. Functional amyloids were discovered in diverse taxa, ranging from bacteria to mammals. These amyloids are involved in vital biological functions such as long-term memory, storage of peptide hormones and scaffolding melanin polymerization in animals, substrate attachment, and biofilm formation in bacteria and fungi, etc. Thus, amyloids undoubtedly are playing important roles in biological and pathological processes. This review is focused on functional amyloids in mammals and summarizes approaches used for identifying new potentially amyloidogenic proteins and domains.

Current Understanding of the Structure, Stability and Dynamic Properties of Amyloid Fibrils

“…There are also functional amyloids playing other roles such as virulence, protection against degradation and adhesion [ 55 , 58 ], as well as in the more complicated regulatory functions in the transcription, heterokaryon incompatibility, and long-term memory, etc. of eukaryotes, as have also been reported [ 56 ]. For amyloid fibrils to exert biological functions, the spatiotemporal regulation of their formation seems to be achieved elaborately.…”

“…It has become increasingly clear that amyloid structures are not only found in aberrant and disease-related aggregates, but also in functional protein assemblies referred to as “functional amyloids” [ 7 ]. Functional amyloids are mainly produced by prokaryotes [ 6 , 55 ] and some of them are produced by higher eukaryotes [ 56 ]. It is currently understood that functional amyloids serve diverse purposes, and some of them act as biofilm matrix proteins playing a scaffolding role in microorganisms [ 6 , 55 ].…”

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

“…Incidentally, these findings can be equated with amyloidosis and autophagy. That is, amyloid deposition and "arrested" basal cells [96,97] equate to amyloidosis as a natural physiological response to stressors of nitric oxide reduction [98,99] and p63overexpression (p53-family) equates to autophagy induction [100].…”

“…Amyloidosis is a natural physiological response in mammalian cells and enables cells to store large quantities of proteins and enter a dormant state in response to stressors (e.g., hypoxia, oxidative stress) [98,99]. The family of serum amyloid A proteins encoding genes have been well conserved throughout vertebrate evolution [102,103].…”

Function, Regulation, and Dysfunction of Intrinsically Disordered Proteins

“…It has also emerged that amyloids are not only pathological accidents but that they can occasionally have a functional relevance. This aspect is discussed in this issue by Rubel and co-workers [ 15 ], overviewing the variety of roles that are currently known for functional amyloids.…”