Amyloid State of Proteins in Human Disease

Abstract

Over 30 human amyloidoses, such as prion disease, Alzheimer's disease and Parkinson's disease, are characterised with the formation of amyloid plagues. Amyloid plagues are the products of protein aggregation, which begins with soluble amyloidogenic proteins into insoluble amyloid fibrils. Mounting evidences suggest that those aggregation processes are noxious to cells, during which the formation of oligomers is believed to be the most toxic species. In vivo , it has been proven that physiological factors have taken part in self‐defence line to reverse or alleviate the damages originated from aggregates. Moreover, therapeutic strategies targeting amyloid formation are also promising to alleviate human amyloidosis. In the present article, amyloid formation pathways, possible damages originated from different species of aggregates, physiological factors involved in self‐defence and therapeutic strategies targeting amyloid formation are summarised. Key Concepts The aggregation of amyloidogenic proteins plays critical roles in over 30 amyloidoses Misfolded monomers, oligomers and fibrils are major species at different stages of aggregation Oligomers are believed to be the most toxic species both in vivo and in vitro Physiological regulations against amyloid aggregations exist in healthy individuals Targeting aggregates of amyloidogenic proteins at different stage could be a potential therapeutic approach to resolve amyloidosis

Controlling Solvent Polarity to Regulate Protein Self-Assembly Morphology and Its Universal Insight for Fibrillation Mechanism

“…The amyloid fibril refers to an insoluble supramolecular structure with a high aspect ratio and ordered characteristics generated by protein self-assembly. 1 The formation of amyloid fibers has been implicated in many neurological diseases, such as Parkinson's, Alzheimer's, Creutzfeldt−Jakob disease, type II diabetes, and bovine spongiform encephalopathy, 2 making the study of the mechanism and conditions of protein selfassembly very interesting. Recently, it was found that many food proteins, such as β-lactoglobulin (β-lg), 3 zein, 4 and soy protein, 5 can also self-assemble into amyloid fibers under certain conditions and even form protein fibers of different sizes and shapes by controlling the temperature, pH, solvent polarity, ionic strength, etc.…”