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. , 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

Keywords: amyloid; amyloidosis; protein aggregation; therapeutic strategy

Figure 1. Morphological characteristics of amyloid plagues and fibrils. (a) Amyloid plagues in AD composed of Aβ protein; (b) a representative AFM images of fibrils formed by hIAPP.
Figure 2. Aggregation process of proteins/peptides.
Figure 3. Structures of small molecular inhibitors. Compounds in upper row belong to polyphenols; phenolic hydroxyl groups are coloured in red; compounds in bottom row belong to non‐polyphenols type with aromatic rings.
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Huang, Lianqi, and Huang, Kun(Nov 2015) Amyloid State of Proteins in Human Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024459]