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: Marin Guentchev, Sandra L Siedlak, Christa Jarius, Fabrizio Tagliavini, Rudy J Castellani, George Perry, Mark A Smith, Herbert Budka
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 9 Issue 3 Pg. 275-81 (Apr 2002) ISSN: 0969-9961 [Print] United States
• PMID: 11950273 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: (c) 2002 Elsevier Science (USA).

Chemical References

• Nucleic Acids

Topics

• Adult
• Aged
• Brain (metabolism, pathology)
• Brain Chemistry
• Female
• Humans
• Male
• Middle Aged
• Nucleic Acids (analysis, biosynthesis)
• Oxidative Stress (physiology)
• Prion Diseases (metabolism, pathology)