Regular Paper

Acta Neuropathologica

, Volume 110, Issue 3, pp 232-238

Redox metals and oxidative abnormalities in human prion diseases

  • Robert B. PetersenAffiliated withInstitute of Pathology, Case Western Reserve University
  • , Sandra L. SiedlakAffiliated withInstitute of Pathology, Case Western Reserve University
  • , Hyoung-gon LeeAffiliated withInstitute of Pathology, Case Western Reserve University
  • , Yong-Sun KimAffiliated withCollege of Medicine, Hallym University
  • , Akihiko NunomuraAffiliated withDepartment of Psychiatry and Neurology, Asahikawa Medical College
  • , Fabrizio TagliaviniAffiliated withIstituto Neurologico Carlo Besta
  • , Bernardino GhettiAffiliated withDepartment of Pathology, Indiana University School of Medicine
  • , Patrick CrasAffiliated withUniversiteits Pleini, Born Bunge Foundation
  • , Paula I. MoreiraAffiliated withCenter for Neuroscience and Cell Biology of Coimbra, University of Coimbra
    • , Rudy J. CastellaniAffiliated withNeuropathology, Michigan State University
    • , Marin GuentchevAffiliated withInstitute of Neurology, Medical University of Vienna and Austrian Reference Center for Human Prion Disease
    • , Herbert BudkaAffiliated withInstitute of Neurology, Medical University of Vienna and Austrian Reference Center for Human Prion Disease
    • , James W. IronsideAffiliated withInstitute of Pathology, Case Western Reserve UniversityCentre for Neuroscience, The University of Edinburgh
    • , Pierluigi GambettiAffiliated withInstitute of Pathology, Case Western Reserve University
    • , Mark A. SmithAffiliated withInstitute of Pathology, Case Western Reserve University
    • , George PerryAffiliated withInstitute of Pathology, Case Western Reserve University Email author 

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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-β, 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.

Keywords

Creutzfeld-Jakob disease Gerstmann-Straussler-Scheinker syndrome Oxidative damage Prion Redox metals