Protein misfolding, aggregation and mechanism of amyloid cytotoxicity: An overview and therapeutic strategies to inhibit aggregation

Abstract Protein and peptides are converted from their soluble forms into highly ordered fibrillar aggregates under various conditions inside the cell. Such transitions confer diverse neurodegenerative diseases including Alzheimer's disease, Huntington's disease Prion's disease, Parkinson's disease, polyQ and share abnormal folding of potentially cytotoxic protein species linked with degeneration and death of precise neuronal populations. Presently, major advances are made to understand and get detailed insight into the structural basis and mechanism of amyloid formation, cytotoxicity and therapeutic approaches to combat them. Here we highlight classifies and summarizes the detailed overview of protein misfolding and aggregation at their molecular level including the factors that promote protein aggregation under in vivo and in vitro conditions. In addition, we describe the recent technologies that aid the characterization of amyloid aggregates along with several models that might be responsible for amyloid induced cytotoxicity to cells. Overview on the inhibition of amyloidosis by targeting different small molecules (both natural and synthetic origin) have been also discussed, that provides important approaches to identify novel targets and develop specific therapeutic strategies to combat protein aggregation related neurodegenerative diseases.