Strategies for inhibiting amyloid fibrillation: Current status and future prospects.

Abstract

One of the hallmarks of multiple neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, is deposition of insoluble amyloid fibrils, which are toxic proteinaceous structures containing cross β-sheets. Several inhibitory strategies have been devised by researchers to impede or slow down the generation of such toxic species. Small compounds, peptides, and antibodies have been studied as possible inhibitors to interfere with key steps in amyloid production. Furthermore, adjusting environmental variables, such as temperature and pH have been known to impact the amyloid fibrillation process. Additionally, strategies are also available to reduce the possibility of protein misfolding so as to inhibit the subsequent development of fibrils, simply by stabilizing native protein conformations. It is very promising to develop targeted inhibitory therapies and comprehend the complexities of amyloid fibrillation in order to develop effective therapeutics to slow the progression of neurodegenerative disorders linked to misfolding and aggregation of proteins.