Abstract
Variant Creutzfeldt-Jakob disease is thought to be caused by
infected prion protein via ingestion of contaminated beef. After ingestion of
infected prion proteins, uptake by small intestine may be by either M-cell
dependent or M-cell independent routes. A receptor for prion protein, laminin
receptor precursor is expressed on the brush border of small intestinal
epithelium in 40 % of subjects. The cellular prion protein
expressed on the enteric nervous system might serve as the target for
conversion to infectious prion protein and a route for spread to the central
nervous system.
Zusammenfassung
Eine Variante der Creutzfeldt-Jakob-Krankheit soll über die
Aufnahme kontaminierten Rindfleischs durch infektiöses Prionenprotein
hervorgerufen werden. Nach dem Verzehr können die Prionenproteine im
Dünndarm durch Vermittlung der M-Zellen oder unabhängig davon
aufgenommen werden. Bei 40 % aller Menschen wird am
Bürstensaum des Dünndarmepithels ein Rezeptor für
Prionenproteine, der Lamininrezeptor, exprimiert. Das im enterischen
Nervensystem exprimierte zelluläre Prionenprotein könnte als Ziel
für die Umwandlung in infektiöses Protein dienen und den Weg zur
Ausbreitung ins Zentralnervensystem darstellen.
Key words
Prions - Variant
CJD - Laminin Receptor Protein - Small Intestine
Schlüsselwörter
Prionen - CJD-Variante - Laminin-Rezeptorprotein - Dünndarm
References
- 1
Prusiner S B.
Novel proteinaceous infectious particles cause
scrapie.
Science.
1982;
216
136-144
- 2
Prusiner S B.
Prions.
Proc Natl Acad
Sci.
1998;
95
13 363-13 383
- 3
Prusiner S B.
Molecular biology of prion
diseases.
Science.
1991;
252
1515-1522
- 4
Harris D A.
Cellular biology of prion diseases.
Clin Microbiol
Rev.
1999;
12
429-444
- 5
Pan K M, Baldwin M, Nguyen J
. et al .
Conversion of alpha-helices into β-sheets features in
the formation of scrapie prion proteins.
Proc Natl Acad
Sci.
1993;
90
10 962-10 966
- 6
Will R G, Ironside J W, Zeidler M
. et al .
A new-variant of Creutzfeldt- Jakob disease in the
UK.
Lancet.
1996;
347
921-925
- 7
Collee J G, Bradley R.
BSE: A decade on-part
I.
Lancet.
1997;
349
636-641
- 8
Ghani A C, Ferguson N M, Donnelly C A, Anderson R M.
Predicted vCJD mortality in Great
Britain.
Nature.
2000;
406
583-584
- 9
Cousens S, Smith P G, Ward H
. et al .
Geographical distribution of variant Creutzfeldt-Jakob
disease in Great Britain,
1996-2000.
Lancet.
2001;
357
1002-1007
- 10
Cohen F E, Prusiner S B.
Pathologic conformations of prion proteins.
Ann Rev
Biochem.
1998;
67
793-819
- 11
Beekes M, McBride P A.
Early accumulation of pathological PrP in the enteric nervous
system and gut-associated lymphoid tissue of hamsters orally infected with
scrapie.
Neurosci
Lett.
2000;
278
181-184
- 12
Rieger R, Edenhofer F, Lasmezas C I, Weiss S.
The human 37-kDa laminin receptor precursor interacts with
the prion protein in eukaryotic cells.
Nat
Med.
1997;
3
1383-1388
- 13
Shmakov A N, Bode J, Kilshaw P J, Ghosh S.
Diverse patterns of expression of the 67-kD laminin receptor
in human small intestinal mucosa: Potential binding sites for prion
proteins.
J
Pathol.
2000;
191
318-322
- 14
Shmakov A N, McLennan N F, McBride P
. et al .
Cellular prion protein is expressed in the human enteric
nervous system.
Nat
Med.
2000;
6
840-841
- 15
Wadsworth J DF, Joiner S, Hill A F
. et al .
Tissue distribution of protease resistant prion protein in
variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting
assay.
Lancet.
2001;
358
171-180
- 16
Ironside J W, Head M W, Bell J E, McCardle L, Will R G.
Laboratory diagnosis of variant Creutzfeldt-Jakob
disease.
Histopathology.
2000;
37
1-9
- 17
Hilton D A, Fathers E, Edwards P, Ironside J W, Zajicek J.
Prion immunoreactivity in appendix before clinical onset of
variant Creutzfeldt-Jakob
disease.
Lancet.
1998;
352
703-704
- 18
Bruce M E, McConnell I, Will R G, Ironside J W.
Detection of variant Creutzfeldt-Jakob disease infectivity in
extraneural
tissues.
Lancet.
2001;
358
208-209
Prof. S. Ghosh
Gastroenterology Section, Imperial College School of
Medicine
Hammersmith Campus
London W12 0NN
Email: s.ghosh@ic.ac.uk