Oxidative damage to nucleic acids in human prion disease

• Published in: Neurobiology of disease Vol. 9; no. 3; pp. 275 - 281
• Main Authors: Guentchev, Marin, Siedlak, Sandra L, Jarius, Christa, Tagliavini, Fabrizio, Castellani, Rudy J, Perry, George, Smith, Mark A, Budka, Herbert
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.04.2002
• Subjects: Adult; Aged; Brain - metabolism; Brain - pathology; Brain Chemistry; Female; Humans; Male; Middle Aged; Nucleic Acids - analysis; Nucleic Acids - biosynthesis; Oxidative Stress - physiology; Prion Diseases - metabolism; Prion Diseases - pathology
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1006/nbdi.2002.0477

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.