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Papers In Press, published online ahead of print June 21, 2001
J. Biol. Chem, 10.1074/jbc.C100278200
Submitted on May 28, 2001
Revised on June 14, 2001
Accepted on June 21, 2001

A protease resistant PrP isoform is present in urine of animals and humans affected with prion diseases

Gideon M. Shaked, Yuval Shaked, Zehavit Kariv, Michele Halimi, Inbal Avraham, and Ruth Gabizon

Neurology, Hadassah University Hospital, Jerusalem 91120

Corresponding Author: gabizonr{at}hadassah.org.il

PrPSc, the only known component of the prion, is present mostly in the brains of animals and humans affected with prion diseases. We now show that a protease resistant PrP isoform can also be detected in the urine of hamsters, cattle and humans suffering from TSEs. Most important, this PrP isoform (UPrPSc) was also found in the urine of hamsters inoculated with prions long before the appearance of clinical signs. Interestingly, i.c. inoculation of hamsters with UPrPSc did not cause clinical signs of prion disease even after 270 days, suggesting it differs in its pathogenic properties from brain PrPSc. We propose that the detection of UPrPSc can be used to diagnose humans and animals incubating prion diseases, as well as to increase our understanding on the metabolism of PrPSc in-vivo.


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