부산대학교 도서관

Prion diseases (PrD) or transmissible spongiform encephalopathies (TSE) are invariably fatal and pathogenic neurodegenerative disorders caused by the self-propagated misfolding of cellular prion protein (PrP.sup.C) to the neurotoxic pathogenic form (PrP.sup.TSE) via a yet undefined but profoundly complex mechanism. Despite several decades of research on PrD, the basic understanding of where and how PrP.sup.C is transformed to the misfolded, aggregation-prone and pathogenic PrP.sup.TSE remains elusive. The primary clinical hallmarks of PrD include vacuolation-associated spongiform changes and PrP.sup.TSE accumulation in neural tissue together with astrogliosis. The difficulty in unravelling the disease mechanisms has been related to the rare occurrence and long incubation period (over decades) followed by a very short clinical phase (few months). Additional challenge in unravelling the disease is implicated to the unique nature of the agent, its complexity and strain diversity, resulting in the heterogeneity of the clinical manifestations and potentially diverse disease mechanisms. Recent advances in tissue isolation and processing techniques have identified novel means of intercellular communication through extracellular vesicles (EVs) that contribute to PrP.sup.TSE transmission in PrD. This review will comprehensively discuss PrP.sup.TSE transmission and neurotoxicity, focusing on the role of EVs in disease progression, biomarker discovery and potential therapeutic agents for the treatment of PrD.
Author(s): Arun Khadka [sup.1], Jereme G. Spiers [sup.1], Lesley Cheng [sup.1], Andrew F. Hill [sup.1] [sup.2] Author Affiliations: (1) grid.1018.8, 0000 0001 2342 0938, Department of Biochemistry & Chemistry, La [...]