Pathology of Protein Misfolding Diseases in Animals

Abstract

Protein misfolding diseases are the diseases, which cause transformation of proteins into beta-sheets, forming amyloid fibrils and resulting in aggregate formations and plaques. A wide horizon for occurrence of protein misfolding diseases, includes temperature, pH, surfactant, hydrophobic interaction etc. plays important role. Extensive studies on pathways for protein misfolding converge to mechanism of seed nucleation hypothesis for protein aggregation and misfolding within the cells. Correct folding of proteins is required for normal functioning of the cells and this is accomplished by presence of protein quality control (PQC) system, which make use of endoplasmic reticulum-associated degradation (ERAD), ubiquitin pathway, autophagy, and molecular chaperones. In addition, extrinsic and intrinsic alteration, however, causes misfolding of the protein. Pathological conditions, such as prion diseases, amyloidosis, lung diseases, cancer occurrences, Tay Sach’s disease, epidermolysis bullosa, and cataract, are repercussion of protein misfolding. Moreover, the diagnosis of protein aggregates and plaques at an initial stage is challenging. Diagnostic techniques Congo red assay, Thioflavin T binding assay, ANS fluorescence assay, antibody dot blot assay, magnetic resonance imaging, and positron emission tomography are applied but are not routinely used. Although newer techniques are being investigated, lack of suitable biomarkers limits the diagnosis for protein fibril deposition.