Document Detail

Epitope scanning indicates structural differences in brain-derived monomeric and aggregated mutant prion proteins related to genetic prion diseases.
MedLine Citation:
PMID:  23808898     Owner:  NLM     Status:  MEDLINE    
Genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia and prion protein cerebral amyloid angiopathy are clinically and neuropathologically distinct neurodegenerative diseases linked to mutations in the PRNP gene encoding the cellular prion protein (PrPC). How sequence variants of PRNP encode the information to specify these disease phenotypes is not known. It is suggested that each mutation produces a misfolded variant of PrPC with specific neurotoxic properties. However, structural studies of recombinant PrP did not detect major differences between wild-type and mutant molecules, pointing to the importance of investigating mutant PrPs from mammalian brains. We used surface plasmon resonance and a slot-blot immunoassay to analyse the antibody-binding profiles of soluble and insoluble PrP molecules extracted from the brains of transgenic mice modelling different prion diseases. By measuring the reactivity of monoclonal antibodies against different PrP epitopes, we obtained evidence of conformational differences between wild-type and mutant PrPs, and among different mutants. We detected structural heterogeneity in both monomeric and aggregated PrP, supporting the hypothesis that the phenotype of genetic prion diseases is encoded by mutant PrP conformation and assembly state.
Laura Tapella; Matteo Stravalaci; Antonio Bastone; Emiliano Biasini; Marco Gobbi; Roberto Chiesa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  454     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-30     Completed Date:  2013-11-04     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  417-25     Citation Subset:  IM    
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MeSH Terms
Antibodies, Monoclonal / chemistry
Brain / metabolism*
Creutzfeldt-Jakob Syndrome / genetics,  metabolism*
Detergents / chemistry
Epitope Mapping
Gerstmann-Straussler-Scheinker Disease / genetics,  metabolism*
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Mutation, Missense
Polymorphism, Genetic
Prions / chemistry,  genetics,  metabolism*
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Sodium Dodecyl Sulfate / chemistry
Surface Plasmon Resonance
Grant Support
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Detergents; 0/Prions; 368GB5141J/Sodium Dodecyl Sulfate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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