title: Oxidative damage to nucleic acids in human prion disease.
abstract: Recently, several studies proposed a physiological role for the cellular prion protein (PrP(c)) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrP(c) homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrP(c) plays a key role in the pathogenesis of these disorders.
authors.affiliation: Institute of Neurology, University of Vienna, Austrian Reference Center for Human Prion Disease (ORPE).
authors.forename: Marin
authors.initials: M
authors.lastname: Guentchev
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Siedlak
authors.forename: Christa
authors.initials: C
authors.lastname: Jarius
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000032:analysis* / Q000096:biosynthesis; D018384:Oxidative Stress / Q000502:physiology; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology*
chemical_list: D009696:Nucleic Acids