Pathways of amyloid fibril formation and protein aggregation.

The main cause of many neurodegenerative diseases and systemic amyloidoses is protein and peptide aggregation and the formation of amyloid fibrils. The study of aggregation mechanisms, the discovery and description of aggregate structures, and a comprehensive understanding of the molecular mechanisms of amyloid formation are of great importance for the diagnostic processes at the molecular level and for the development of therapeutic strategies to counter aggregation-associated disorders. Given that understanding protein misfolding phenomena is directly related to the protein folding process, we will briefly explain the protein folding mechanism and then discuss the important factors involved in protein aggregation. In the following, we review different mechanisms of amyloid formation and finally represent the current knowledge on how amyloid fibrils are formed based on kinetic and thermodynamic factors.

Inhibitors of amyloid fibril formation.

Many diseases are caused by misfolded and denatured proteins, leading to neurodegenerative diseases. In recent decades researchers have developed a variety of compounds, including polymeric inhibitors and natural compounds, antibodies, and chaperones, to inhibit protein aggregation, decrease the toxic effects of amyloid fibrils, and facilitate refolding proteins. The causes and mechanisms of amyloid formation are still unclear, and there are no effective treatments for Amyloid diseases. This section describes research and achievements in the field of inhibiting amyloid accumulation and also discusses the importance of various strategies in facilitating the removal of aggregates species (refolding) in the treatment of neurological diseases such as chemical methods like as, small molecules, metal chelators, polymeric inhibitors, and nanomaterials, as well as the use of biomolecules (peptide and, protein, nucleic acid, and saccharide) as amyloid inhibitors, are also highlighted.

Functional amyloids.

While amyloid has traditionally been viewed as a harmful formation, emerging evidence suggests that amyloids may also play a functional role in cell biology, contributing to normal physiological processes that have been conserved throughout evolution. Functional amyloids have been discovered in several creatures, spanning from bacteria to mammals. These amyloids serve a multitude of purposes, including but not limited to, forming biofilms, melanin synthesis, storage, information transfer, and memory. The functional role of amyloids has been consistently validated by the discovery of more functional amyloids, indicating a conceptual convergence. The biology of amyloids is well-represented by non-pathogenic amyloids, given the numerous ones already identified and the ongoing rate of new discoveries. In this chapter, functional amyloids in microorganisms, animals, and plants are described.