Amyloidosis-history and development, emphasis on insulin and prion amyloids

Abstract

Amyloidosis is associated with misfolding of protein (normal functional and cellular) into intractable aggregates, commonly known as amyloid fibrils. These amyloid fibrils contain thread-like structure with a high amount of β sheet content and their accumulation initiates the formation of toxic intermediates in the process of self-assembly. This conversion into intractable aggregates is strongly linked with disorders like Creutzfeldt-Jakob disease, Alzheimer's disease, Parkinson's disease, and lifestyle-related Type II diabetes. The exact mechanism of such normal cellular protein conversion into intractable protease-resistant amyloid aggregates has not yet been explored very well, but an agent that can degrade such amyloid fibrils can be a suitable drug candidate for such disorders. Various proteins and peptides like β-amyloid peptide, β2-microglobulin, insulin amyloids (IA), prion, and serum amyloid Aβ protein accumulate in the human body under different diseased conditions. These amyloids have mutual traits and are usually protease-resistant which makes them difficult to clear from the human body. In this review, we have discussed the history of amyloidosis, the different types of amyloids related to neurological disorders, and systemic and localized amyloidosis. A detailed description of insulin amyloids and prion amyloids has been discussed. A glimpse of the use of natural enzymes and their role is the dissociation of amyloids has been discussed.

Keywords

• Amyloidosis
• Systemic and localized amyloidosis
• Insulin amyloids
• Prion peptide aggregation
• Serine proteases