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Redox metals and oxidative abnormalities in human prion diseases

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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.

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Authors and Affiliations

  1. Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106, USA

    Robert B. Petersen, Sandra L. Siedlak, Hyoung-gon Lee, Pierluigi Gambetti, Mark A. Smith & George Perry

  2. College of Medicine, Hallym University, Gangwon-do, Korea

    Yong-Sun Kim

  3. Department of Psychiatry and Neurology, Asahikawa Medical College, 078-8510, Asahikawa, Japan

    Akihiko Nunomura

  4. Istituto Neurologico Carlo Besta, Milano, Italy

    Fabrizio Tagliavini

  5. Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Bernardino Ghetti

  6. Universiteits Pleini, Born Bunge Foundation, Wilrijk, Belgium

    Patrick Cras

  7. Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal

    Paula I. Moreira

  8. Neuropathology, Michigan State University, East Lansing, Michigan, USA

    Rudy J. Castellani

  9. Institute of Neurology, Medical University of Vienna and Austrian Reference Center for Human Prion Disease, Vienna, Austria

    Marin Guentchev & Herbert Budka

  10. Centre for Neuroscience, The University of Edinburgh, Edinburgh, Scotland

    James W. Ironside

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  1. Robert B. Petersen
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  11. Marin Guentchev
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Correspondence to George Perry.

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Petersen, R.B., Siedlak, S.L., Lee, Hg. et al. Redox metals and oxidative abnormalities in human prion diseases. Acta Neuropathol 110, 232–238 (2005). https://doi.org/10.1007/s00401-005-1034-4

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  • DOI: https://doi.org/10.1007/s00401-005-1034-4

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