Proteomic profiling of PrP27-30-enriched preparations extracted from the brain of hamsters with experimental scrapie

Alessandra Giorgi, Laura Di Francesco, Serena Principe, Giuseppina Mignogna, Lau Sennels, Carmine Mancone, Tonino Alonzi, Marco Sbriccoli, Angela De Pascalis, Juri Rappsilber, Franco Cardone, Maurizio Pocchiari, Bruno Maras, M. Eugenia Schinina

Research output: Contribution to journalArticle

Abstract

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders characterized by the accumulation in the CNS of a pathological conformer (PrPTSE) of the host-encoded cellular prion protein (PrPC). PrPTSE has a central role in the pathogenesis of the disease but other factors are likely involved in the pathological process. In this work we employed a multi-step proteomic approach for the identification of proteins that co-purify with the protease-resistant core of PrPTSE (PrP27-30) extracted from brains of hamsters with experimental scrapie. We identified ferritin, calcium/calmodulin-dependent protein kinase α type II, apolipoprotein E, and tubulin as the major components associated with PrP27-30 but also trace amounts of actin, cofilin, Hsp90α, the γ subunit of the T-complex protein 1, glyceraldehyde 3-phosphate dehydrogenase, histones, and keratins. Whereas some of these proteins (tubulin and ferritin) are known to bind PrP, other proteins (calcium/calmodulin-dependent protein kinase α type II, Hsp90α) may associate with PrPTSE fibrils during disease. Apolipoprotein E and actin have been previously observed in association with PrPTSE, whereas cofilin and actin were shown to form abnormal rods in the brain of patients with Alzheimer disease. The roles of these proteins in the development of brain lesions are still unclear and further work is needed to explain their involvement in the pathogenesis of TSEs.

Original languageEnglish
Pages (from-to)3802-3814
Number of pages13
JournalProteomics
Volume9
Issue number15
DOIs
Publication statusPublished - Aug 2009

Keywords

  • FT-ICR
  • MALDI-TOF/TOF
  • Prion protein
  • PrP27-30
  • Transmissible spongiform encephalopathies

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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  • Cite this

    Giorgi, A., Di Francesco, L., Principe, S., Mignogna, G., Sennels, L., Mancone, C., Alonzi, T., Sbriccoli, M., De Pascalis, A., Rappsilber, J., Cardone, F., Pocchiari, M., Maras, B., & Schinina, M. E. (2009). Proteomic profiling of PrP27-30-enriched preparations extracted from the brain of hamsters with experimental scrapie. Proteomics, 9(15), 3802-3814. https://doi.org/10.1002/pmic.200900085