Amyloid Oligomers, Protofibrils and Fibrils

Abstract

Amyloid diseases are of major concern all over the world due to a number of factors including: (i) aging population, (ii) increasing life span and (iii) lack of effective pharmacotherapy options. The past decade has seen intense research in discovering disease-modifying multi-targeting small molecules as therapeutic options. In recent years, targeting the amyloid cascade has emerged as an attractive strategy to discover novel neurotherapeutics. Formation of amyloid species, with different degrees of solubility and neurotoxicity is associated with the gradual decline in cognition leading to dementia/cell dysfunction. Here, in this chapter, we have described the recent scenario of amyloid diseases with a great deal of information about the structural features of oligomers, protofibrils and fibrils. Also, comprehensive details have been provided to differentiate the degree of toxicity associated with prefibrillar aggregates. Moreover, a review of the technologies that aid characterisation of oligomer, protofibrils and fibrils as well as various inhibition strategies to overcome protein fibrillation are also discussed.

Keywords: Alzheimer’ disease; Amyloid; Cell toxicity; Prefibrillar aggregates.