Trafficking and degradation pathways in pathogenic conversion of prions and prion-like proteins in neurodegenerative diseases

Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. Despite differences in the primary structure and subcellular localization of these proteins, which include the prion protein, a-synuclein and amyloid precursor protein (APP), striking similarity has been observed in their ability to seed and convert naive protein molecules as well as transfer between cells. This review aims to cover what is known about the intracellular trafficking of these proteins as well as their degradation mechanisms and highlight similarities in their movement through the endocytic pathway that could contribute to the pathogenic conversion and seeding of these proteins which underlies the basis of these diseases. (C) 2015 Elsevier B.V. All rights reserved.