title: Redox metals and oxidative abnormalities in human prion diseases.
abstract: Prion diseases are characterized by the accumulation of diffuse and aggregated plaques of protease-resistant prion protein (PrP) in the brains of affected individuals and animals. Whereas prion diseases in animals appear to be almost exclusively transmitted by infection, human prion diseases most often occur sporadically and, to a lesser extent, by inheritance or infection. In the sporadic cases (sporadic Creutzfeld-Jakob disease, sCJD), PrP-containing plaques are infrequent, whereas in transmitted (variant CJD) and inherited (Gerstmann-Straussler-Scheinker Syndrome) cases, plaques are a usual feature. In the current study, representative cases from each of the classes of human prion disease were analyzed for the presence of markers of oxidative damage that have been found in other neurodegenerative diseases. Interestingly, we found that the pattern of deposition of PrP, amyloid-beta, and redox active metals was distinct for the various prion diseases. Whereas 8-hydroxyguanosine has been shown to be increased in sCJD, and inducible NOS is increased in scrapie-infected mice, well-studied markers of oxidative damage that accumulate in the lesions of other neurodegenerative diseases (such as Alzheimer's disease, progressive supranuclear palsy, and Parkinson's disease), such as heme oxygenase-1 and lipid peroxidation, were not found around PrP deposits or in vulnerable neurons. These findings suggest an important distinction in prion-related oxidative stress, indicating that different neurodegenerative pathways are involved in different prion diseases.
authors.affiliation: Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Siedlak
authors.forename: Hyoung-gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: Marin
authors.initials: M
authors.lastname: Guentchev
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D008670:Metals / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D011328:Prions / Q000032:analysis / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D008670:Metals; D011328:Prions; D006151:Guanosine; C046215:8-hydroxyguanosine; D052247:Nitric Oxide Synthase Type II