NR ACNV
AU Chen,S.G.; Parchi,P.; Brown,P.; Capellari,S.; Zou,W.Q.; Cochran,E.J.; Vnencak-Jones,C.L.; Julien,J.; Vital,C.; Mikol,J.; Lugaresi,E.; Autilio-Gambetti,L.; Gambetti,P.
TI Allelic origin of the abnormal prion protein isoform in familial prion diseases
QU Nature Medicine 1997 Sep; 3(9): 1009-15
PT journal article
AB The hallmark of prion diseases is the presence of an aberrant isoform of the prion protein (PrPres) that is insoluble in nondenaturing detergents and resistant to proteases. We investigated the allelic origin of PrPres in brains of subjects heterozygous for the D178N mutation linked to fatal familial insomnia (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD178), as well as for insertional mutations associated with another CJD subtype. We found that in FFI and CJD178 subjects, only mutant PrP was detergent-insoluble and protease-resistant. Therefore, PrPres derives exclusively from the mutant allele carrying the D178N mutation. In contrast, in the CJD subtype harboring insertional mutations, wild-type PrP was also detergent-insoluble and likely to be protease-resistant. Our findings indicate that the participation of the wild-type PrP in the formation of PrPres depends on the type of mutations, providing an insight into the molecular mechanisms underlying the phenotypic heterogeneity in familial prion diseases.
IN In Gehirnen von Menschen mit der fatalen familiären Schlaflosigkeit oder der D178N-Creutzfeldt-Jakob-Krankheit wurde unter den unlöslichen und proteaseresistenten Prionproteinen nur solche mit der pathogenen Mutation gefunden, während die Wildtyp Prionproteine offenbar nicht in den Polymerisationsprozeß einbezogen wurden. Hingegen waren bei einem Creutzfeldt-Jakob-Patienten mit einer Insertionsmutation in einem Allel, auch Wildtyp-Prionproteine unlöslich und wahrscheinlich proteaseresistent.
ZR 45
MH *Alleles; Comparative Study; Creutzfeldt-Jakob Syndrome/classification/genetics; Detergents; Endopeptidases; Heterozygote; Human; Mutation; Peptide Mapping; Phenotype; Point Mutation; Prion Diseases/*genetics; Prions/*genetics/isolation & purification; Sleep Initiation and Maintenance Disorders/genetics; Solubility; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Shu G. Chen, Piero Parchi, Sabina Capellari, Wen-Quan Zou, Lucila Autilio-Gambetti & Pierluigi Gambetti, Division of Neuropathology, Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road,Cleveland, Ohio 44106, USA; Paul Brown, Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA; Elizabeth J. Cochran, Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Chicago, Illinois 60612, USA; Cindy L. Vnencak-Jones, Department of Pathology, Vanderbilt University Medical Center, 1301 22nd Avenue South, Nashville, Tennessee 37232, USA; Jean Julien, Claude Vital, Departments of Neurology and Pathology, CHU Bordeaux, Avenue de Magellan, 33604 Pessac, France; Jacqueline Mikol, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris, France; Elio Lugaresi, Neurological Institute, University of Bologna, Via U. Foscolo 7, 40123 Bologna, Italy; Correspondence should be addressed to S.G.C. or P.G.
SP englisch
PO USA
OR Prion-Krankheiten C