Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patients

被引:56
作者
Silvestrini, MC
Cardone, F
Maras, B
Pucci, P
Barra, D
Brunori, M
Pocchiari, M
机构
[1] IST SUPER SANITA,VIROL LAB,I-00161 ROME,ITALY
[2] CNR,CTR MOL BIOL,I-00185 ROME,ITALY
[3] UNIV NAPLES,DIPARTIMENTO CHIM ORGAN & BIOL,I-80134 NAPLES,ITALY
[4] UNIV ROMA LA SAPIENZA,DIPARTIMENTO SCI BIOCHIM A ROSSI FANELLI,I-00185 ROME,ITALY
关键词
D O I
10.1038/nm0597-521
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A characteristic feature of Creutzfeldt-jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. 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 (Val210Ile), 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.
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页码:521 / 525
页数:5
相关论文
共 47 条
[1]   Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Straussler-Scheinker disease (PrP-P102L mutation) [J].
Barbanti, P ;
Fabbrini, G ;
Salvatore, M ;
Petraroli, R ;
Cardone, F ;
Maras, B ;
Equestre, M ;
Macchi, G ;
Lenzi, GL ;
Pocchiari, M .
NEUROLOGY, 1996, 47 (03) :734-741
[2]   HUMAN SPONGIFORM ENCEPHALOPATHY - THE NATIONAL-INSTITUTES-OF-HEALTH SERIES OF 300 CASES OF EXPERIMENTALLY TRANSMITTED DISEASE [J].
BROWN, P ;
GIBBS, CJ ;
RODGERSJOHNSON, P ;
ASHER, DM ;
SULIMA, MP ;
BACOTE, A ;
GOLDFARB, LG ;
GAJDUSEK, DC .
ANNALS OF NEUROLOGY, 1994, 35 (05) :513-529
[3]   IATROGENIC CREUTZFELDT-JAKOB-DISEASE - AN EXAMPLE OF THE INTERPLAY BETWEEN ANCIENT GENES AND MODERN MEDICINE [J].
BROWN, P ;
CERVENAKOVA, L ;
GOLDFARB, LG ;
MCCOMBIE, WR ;
RUBENSTEIN, R ;
WILL, RG ;
POCCHIARI, M ;
MARTINEZLAGE, JF ;
SCALICI, C ;
MASULLO, C ;
GRAUPERA, G ;
LIGAN, J ;
GAJDUSEK, DC .
NEUROLOGY, 1994, 44 (02) :291-293
[4]   MICE DEVOID OF PRP ARE RESISTANT TO SCRAPIE [J].
BUELER, H ;
AGUZZI, A ;
SAILER, A ;
GREINER, RA ;
AUTENRIED, P ;
AGUET, M ;
WEISSMANN, C .
CELL, 1993, 73 (07) :1339-1347
[5]   NORMAL DEVELOPMENT AND BEHAVIOR OF MICE LACKING THE NEURONAL CELL-SURFACE PRP PROTEIN [J].
BUELER, H ;
FISCHER, M ;
LANG, Y ;
BLUETHMANN, H ;
LIPP, HP ;
DEARMOND, SJ ;
PRUSINER, SB ;
AGUET, M ;
WEISSMANN, C .
NATURE, 1992, 356 (6370) :577-582
[6]   A KINETIC-MODEL FOR AMYLOID FORMATION IN THE PRION DISEASES - IMPORTANCE OF SEEDING [J].
COME, JH ;
FRASER, PE ;
LANSBURY, PT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :5959-5963
[7]   PREDISPOSITION OF PRION PROTEIN HOMOZYGOTES TO CREUTZFELDT-JAKOB-DISEASE CAN BE EXPLAINED BY A NUCLEATION-DEPENDENT POLYMERIZATION MECHANISM [J].
COME, JH ;
LANSBURY, PT .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (09) :4109-4110
[8]   THE NATURE OF THE SCRAPIE AGENT - THE VIRUS THEORY [J].
DIRINGER, H ;
BEEKES, M ;
OBERDIECK, U .
SLOW INFECTIONS OF THE CENTRAL NERVOUS SYSTEM: THE LEGACY OF DR BJORN SIGURDSSON, 1994, 724 :246-258
[9]   CHARACTERIZATION OF A TRANSTHYRETIN (PREALBUMIN) VARIANT ASSOCIATED WITH FAMILIAL AMYLOIDOTIC POLYNEUROPATHY TYPE-II (INDIANA SWISS) [J].
DWULET, FE ;
BENSON, MD .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (04) :880-886
[10]  
Eaton W A, 1990, Adv Protein Chem, V40, P63, DOI 10.1016/S0065-3233(08)60287-9