Nature Medicine
3, 521 - 525 (1997)
doi:10.1038/nm0597-521
Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patientsMaria Chiara Silvestrini1, †, Franco Cardone2, Bruno Maras1, Piero Pucci3, Donatella Barra1, Maurizio Brunori1
& Maurizio Pocchiari2
1Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Universita di Roma "La Sapienza," and Centra di Biologia Molecolare del Consiglio Nazionale delle Ricerche, Piazzale Aldo Moro 5, 00185 Rome, Italy
2Laboratorio di Virologia, Istituto Superiors di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
3Dipartimento di Chimica Organica e Biologica, Università di Napoli "Federico II," 80134 Naples, Italy
†Deceased, see Acknowledgements. A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPsen. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methionine or valine residue at the polymorphic position 129 may be critical in sporadic CJD cases. We found that in the brain of patients heterozygous for the mutation in which isoleucine is substituted for valine at codon 210 (Val210lle), the PrPres is formed by both the wild-type and mutant PrPsen. We also found that in a sporadic CJD patient, who was heterozygous (Met/Val) at position 129, PrPres is also formed by both allotypes. These data associate transmissible spongiform encephalopathies with other amyloidosis, although the nature of the transmissible agent remains unsettled.
REFERENCES
- Pocchiari, M. Prions and related neurological diseases. Mol. Aspects Med. 15, 195−291 (1994). | Article | PubMed | ISI | ChemPort |
- Oesch, B. et al. A cellular gene encodes scrapie PrP 27-30 protein. Cell 40, 735−746 (1985). | Article | PubMed | ISI | ChemPort |
- Stahl, N. et al. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry 32, 1991−2002 (1993). | PubMed | ISI | ChemPort |
- Pan, K.M. et al. Conversion of
 -helices into  -sheets features in the formation of the scrapie prion proteins. Proc. Natl. Acad. Sci. USA 90, 10962−10966 (1993). | PubMed | ChemPort |
- Büeler, H. et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356, 577−582 (1992). | Article | PubMed | ISI | ChemPort |
- Büeler, H. et al. Mice devoid of PrP are resistant to scrapie. Cell 73, 1339−1347 (1993). | Article | PubMed | ISI | ChemPort |
- Xi, Y.G., Ingrosso, L., Ladogana, A., Masullo, C. & Pocchiari, M. Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation. Nature 356, 598−601 (1992). | Article | PubMed | ISI | ChemPort |
- Prusiner, S.B. Inherited prion diseases. Proc. Natl. Acad. Sci. USA 91, 4611−4614 (1994). | PubMed | ChemPort |
- Mastrianni, J.A. Lannicola, C. Myers, R.M. DeArmond, S. & Prusiner, S.B. Mutation of the prion protein gene at codon 208 in familial Creutzfeldt-Jakob disease. Neurology 47, 1305−1312 (1996). | PubMed | ISI | ChemPort |
- Goldfarb, L.G. & Brown, P. The transmissible spongiform encephalopathies. Annu. Rev. Med. 46, 57−65 (1995). | Article | PubMed | ISI | ChemPort |
- Masullo, C., Salvatore, M., Macchi, G., Genuardi, M. & Pocchiari, M. Progressive dementia in a young patient with a homozygous deletion of the PrP gene. Ann. N. Y. Acad. Sci. 724, 358−360 (1994). | PubMed | ISI | ChemPort |
- Salvatore, M. et al. Polymorphisms of the prion protein gene in Italian patients with Creutzfeldt-Jakob disease. Hum. Genet. 94, 375−379 (1994). | PubMed | ISI | ChemPort |
- Brown, P. et al. Human spongiform encephalopathy: The National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann. Neurol. 35, 513−529 (1994). | PubMed | ISI | ChemPort |
- Tateishi, J. et al. First experimental transmission of fatal familial insomnia. Nature 376, 434−435 (1995). | Article | PubMed | ISI | ChemPort |
- Windl, O. et al. Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: A systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum. Genet. 98, 259−264 (1996). | Article | PubMed | ISI | ChemPort |
- Goldfarb, L.G. et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Disease phenotype determined by a DNA polymorphism. Science 258, 806−808 (1992). | PubMed | ISI | ChemPort |
- Pocchiari, M. et al. A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease. Ann. Neurol. 34, 802−807 (1993). | PubMed | ISI | ChemPort |
- Barbanti, P. et al. Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Strässler-Scheinker disease (PrP-P102L mutation). Neurology 47, 734−741 (1996). | PubMed | ISI | ChemPort |
- Furukawa, H., Kitamoto, T., Tanaka, Y. & Tateishi, J. New variant prion protein in a Japanese family with Gerstmann-Sträusler syndrome. Mol. Brain Res. 30, 385−388 (1995). | Article | PubMed | ISI | ChemPort |
- Petraroli, R. & Pocchiari, M. Codon 219 polymorphism of PRNP in healthy Caucasians and Creutzfeldt-Jakob disease patients. Am. J. Hum. Genet. 58, 888−889 (1996). | PubMed | ISI | ChemPort |
- Prusiner, S.B. Biology and genetics of prion diseases. Annu. Rev. Microbiol. 48, 655−686 (1994). | Article | PubMed | ISI | ChemPort |
- Weissmann, C. Molecular biology of transmissible spongiform encephalopathies. FEBS Lett. 389, 3−11 (1996). | Article | PubMed | ISI | ChemPort |
- Telling, G.C. et al. Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83, 79−90 (1995). | Article | PubMed | ISI | ChemPort |
- Weissmann, C. A 'unified theory' of prion propagation. Nature 352, 679−683 (1991). | Article | PubMed | ISI | ChemPort |
- Diringer, H., Beekes, M. & Oberdieck, U. The nature of the scrapie agent: The virus theory. Ann. N. Y. Acad. Sci. 724, 246−258 (1994). | PubMed | ISI | ChemPort |
- Kitamoto, T., Yamaguchi, K., Doh-ura, K. & Tateishi, J.A. A prion protein missense variant is integrated in kuru plaque cores in patients with Gerstmann-Straussler syndrome. Neurology 41, 306−310 (1991). | PubMed | ISI | ChemPort |
- Tagliavini, F. et al. Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele. Cell 79, 695−703 (1994). | PubMed | ISI | ChemPort |
- Gabizon, R. et al. Insoluble wild-type and protease-resistant mutant prion protein in brains of patients with inherited prion disease. Nature Med. 2, 59−64 (1996). | Article | PubMed | ISI | ChemPort |
- Ghetti, B. et al. Vascular variant of prion protein cerebral amyloidosis with T-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP. Proc. Natl. Acad. Sci. USA 93, 744−748 (1996). | Article | PubMed | ChemPort |
- Prelli, F. et al. Expression of a normal and variant Alzheimer's -protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. Biochem. Biophys. Res. Commun. 170, 301−307 (1990). | PubMed | ISI | ChemPort |
- Tawara, S., Nakazato, M., Kangawa, K., Matsuo, H. & Araki, S. Identification of amyloid prealbumin in familial amyloidotic polyneuropathy (Japanese type). Biochem. Biophys. Res. Commun. 116, 880−888 (1983). | PubMed | ISI | ChemPort |
- Saraiva, M.J.M., Birken, S., Costa, P.P. & Goodman, D.S. Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. J. Clin. Invest. 74, 104−119 (1984). | PubMed | ISI | ChemPort |
- Dwulet, F.E. & Benson, M.D. Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin. Proc. Natl. Acad. Sci. USA 81, 694−698 (1984). | PubMed | ChemPort |
- Dwulet, F.E. & Benson, M.D. Characterization of a transthyretin (prealbumin) variant associated with familial amyloidotic polyneuropathy type II (Indiana/Swiss). J. Clin. Invest. 78, 880−886 (1986). | PubMed | ISI | ChemPort |
- Westermark, P., Sletten, K. & Olofsson, B.O. Prealbumin variants in the amyloid fibrils of Swedish familial amyloidotic polyneuropathy. Clin. Exp. Immunol. 69, 695−701 (1987). | PubMed | ISI | ChemPort |
- Gajdusek, D.C. Spontaneous generation of infectious nucleating amyloids in the transmissible and nontransmissible cerebral amyloidoses. Mol. Neurobiol. 8, 1−13 (1994). | PubMed | ISI | ChemPort |
- Jarrett, J.T. & Lansbury, P.T.Jr. Seeding "one-dimensional crystallization" of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73, 1055−1058 (1993). | PubMed | ISI | ChemPort |
- Eaton, W.A. & Hofrichter, J. Sickle cell hemoglobin polymerization. Adv. Protein Chem. 40, 63−279 (1990). | PubMed | ChemPort |
- Goldfarb, L.G. et al. Synthetic peptides corresponding to different mutated regions of the amyloid gene in familial Creutzfeldt-Jakob disease show enhanced in vitro formation of morphologically different amyloid fibrils. Proc. Natl. Acad. Sci. USA 90, 4451−4454 (1993). | PubMed | ChemPort |
- Gasset, M. et al. Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. Proc. Natl. Acad. Sci. USA 89, 10940−10944 (1992). | PubMed | ChemPort |
- Riek, R. et al. NMR structure of the mouse prion protein domain PrP(121-231). Nature 382, 180−182 (1996). | Article | PubMed | ISI | ChemPort |
- Brown, P. et al. latrogenic Creutzfeldt-jakob disease: An example of the interplay between ancient genes and modern medicine. Neurology 44, 291−293 (1994). | PubMed | ISI | ChemPort |
- Come, J.H., Fraser, P.E. & Lansbury, P.T.Jr. A kinetic model for amyloid formation in the prion diseases: Importance of seeding. Proc. Natl. Acad. Sci. USA 90, 5959−5963 (1993). | PubMed | ChemPort |
- Come, J.H. & Lansbury, P.T., Jr. Predisposition of prion protein homozygotes to Creutzfeldt-Jakob disease can be explained by a nucleation-dependent polymerization mechanism. J. Am. Chem. Sac. 116, 4109−4110 (1994). | ChemPort |
- Manuelidis, L. & Fritch, W. Infectivity and host responses in Creutzfeldt-Jakob disease. Virology 216, 46−59 (1996). | Article | PubMed | ISI | ChemPort |
- Xi, Y.G., Cardone, F. & Pocchiari, M. Detection of proteinase-resistant protein (PrP) in small brain tissue samples from Creutzfeldt-Jakob disease patients. J. Neurol. Sci. 124, 171−173 (1994). | Article | PubMed | ISI | ChemPort |
- Kascsak, R.J. et al. Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. J. Virol. 59, 676−683 (1986). | PubMed | ISI | ChemPort |
- Kretzschmar, H.A. et al. Molecular cloning of a human prion protein cDNA. DNA 5, 315−324 (1986). | PubMed | ISI | ChemPort |
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