Prions, transmissible spongiform encephalopathies, neurodegeneration, protein misfolding, tau
Abstract
mwymwAbstract:Prion diseases, also known as transmissible spongiform encephalopathies, are universally lethal neurodegenerative disorders associated with the misfolding of the cellular prion protein into its pathological isoform. This arises through the ability of the misfolded protein to induce conformational changes in normally folded proteins, thereby initiating aggregation processes and neurodegenerative events. Very recent investigations have shown that such prion-like mechanisms are not limited to classic prion diseases but also play a role in the pathogenesis of neurodegenerative diseases (NDDs), including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Protein misfolding, aggregation, and the spreading of such proteins as amyloid-β, tau, and α-synuclein are related to the mechanisms of prion propagation, therefore accelerating disease. This review outlines the molecular pathways underlying prion misfolding, aggregation, and cell-to-cell transmission, focusing on state-of-the-art therapeutic strategies that interfere with these processes. Recent advancements in diagnostic techniques have, in particular, given great boosts to the presymptomatic diagnosis of prion diseases by means of the RT-QuIC assay. It concludes with a discussion of how further research into prion-like mechanisms may provide new therapeutic strategies for a wide array of NDDs.
