title: The stress of prion disease.
abstract: Prion diseases are fatal neurodegenerative disorders that include scrapie of sheep, bovine spongiform encephalopathy of cattle, chronic wasting disease of cervids, and Creutzfeldt-Jakob disease (CJD) of humans. The etiology for prion diseases can be infectious, sporadic, or hereditary. However, the common denominator for all types is the formation of a transmissible agent composed of a β-sheet-rich, misfolded version of the host-encoded prion protein (PrPC), known as PrPSc. PrPScself-replicates through a template-assisted process that converts the α-helical conformation of PrPCinto the disease-associated isoform. In parallel with PrPScaccumulation, spongiform change is pathologically observed in the central nervous system, where "holes" appear because of massive neuronal death. Here, we review the cellular pathways triggered in response to PrPScformation and accumulation. Available data suggest that neuronal dysfunction and death may be caused by what originates as a cellular pro-survival response to chronic PrPScaccumulation. We also discuss what is known about the complex cross-talk between the endoplasmic reticulum stress components and the quality control pathways. Better knowledge about these processes may lead to innovative therapeutic strategies based on manipulating the stress response and its consequences for neurodegeneration. This article is part of a Special Issue entitled SI:ER stress.
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mays
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA. Electronic address: Claudio.Soto@uth.tmc.edu.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D017096:Prion Diseases / Q000473:pathology* / Q000503:physiopathology*; D000072002:Prion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000072002:Prion Proteins
keywords: Endoplasmic reticulum stress; Molecular chaperones; Prion; Unfolded protein response