Molecular and clinical insights into protein misfolding and associated amyloidosis

Abstract

The misfolding of normally soluble proteins causes their aggregation and deposition in the tissues which disrupts the normal structure and function of the corresponding organs. The proteins with high β-sheet contents are more prone to form amyloids as they exhibit high propensity of self-aggregation. The self aggregated misfolded proteins act as template for further aggregation that leads to formation of protofilaments and eventually amyloid fibrils. More than 30 different types of proteins are known to be associated with amyloidosis related diseases. Several aspects of the amyloidogenic behavior of proteins remain elusive. The exact reason that causes misfolding of the protein and its association into amyloid fibrils is not known. These misfolded intermediates surpass the over engaged quality control system of the cell which clears the misfolded intermediates. This promotes the self-aggregation, accumulation and deposition of these misfolded species in the form of amyloids in the different parts of the body. The amyloid deposition can be localized as in Alzheimer disease or systemic as reported in most of the amyloidosis. The amyloidosis can be of acquired type or familial. The current review aims at bringing together recent updates and comprehensive information about protein amyloidosis and associated diseases at one place.

Keywords: Amyloid diseases; Amyloidosis; Protein biochemistry; Protein misfolding.