title: Proteomic profiling of PrP27-30-enriched preparations extracted from the brain of hamsters with experimental scrapie.
abstract: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders characterized by the accumulation in the CNS of a pathological conformer (PrP(TSE)) of the host-encoded cellular prion protein (PrP(C)). PrP(TSE) 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 PrP(TSE) (PrP27-30) extracted from brains of hamsters with experimental scrapie. We identified ferritin, calcium/calmodulin-dependent protein kinase alpha type II, apolipoprotein E, and tubulin as the major components associated with PrP27-30 but also trace amounts of actin, cofilin, Hsp90alpha, the gamma 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 alpha type II, Hsp90alpha) may associate with PrP(TSE) fibrils during disease. Apolipoprotein E and actin have been previously observed in association with PrP(TSE), 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.
authors.affiliation: Dipartimento di Scienze Biochimiche, "Sapienza" University of Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giorgi
authors.forename: Laura
authors.initials: L
authors.lastname: Di Francesco
authors.forename: Serena
authors.initials: S
authors.lastname: Principe
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mignogna
authors.forename: Lau
authors.initials: L
authors.lastname: Sennels
authors.forename: Carmine
authors.initials: C
authors.lastname: Mancone
authors.forename: Tonino
authors.initials: T
authors.lastname: Alonzi
authors.forename: Marco
authors.initials: M
authors.lastname: Sbriccoli
authors.forename: Angela
authors.initials: A
authors.lastname: De Pascalis
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Franco
authors.initials: F
authors.lastname: Cardone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.forename: Bruno
authors.initials: B
authors.lastname: Maras
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Schininà
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000032:analysis / Q000378:metabolism; D006224:Cricetinae; D018622:PrP 27-30 Protein / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D012608:Scrapie / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001057:Apolipoproteins E; D011506:Proteins; D018622:PrP 27-30 Protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2