TY - JOUR
T1 - Transgenic over-expression of mammalian heparanase delays prion disease onset and progression
AU - Kovalchuk Ben-Zaken, O.
AU - Nissan, I.
AU - Tzaban, S.
AU - Taraboulos, A.
AU - Zcharia, E.
AU - Matzger, S.
AU - Shafat, I.
AU - Vlodavsky, I.
AU - Tal, Y.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/8/7
Y1 - 2015/8/7
N2 - Abstract Cellular heparan sulfate (HS) has a dual role in scrapie pathogenesis; it is required for PrPSc (scrapie prion protein) formation and facilitates infection of cells, mediating cellular uptake of prions. We examined the involvement of heparanase, a mammalian endoglycosidase degrading HS, in scrapie infection. In cultured cells, heparanase treatment or over-expression resulted in a profound decrease in PrPSc. Moreover, disease onset and progression were dramatically delayed in scrapie infected transgenic mice over-expressing heparanase. Together, our results provide direct in vivo evidence for the involvement of intact HS in the pathogenesis of prion disease and the protective role of heparanase both in terms of susceptibility to infection and disease progression.
AB - Abstract Cellular heparan sulfate (HS) has a dual role in scrapie pathogenesis; it is required for PrPSc (scrapie prion protein) formation and facilitates infection of cells, mediating cellular uptake of prions. We examined the involvement of heparanase, a mammalian endoglycosidase degrading HS, in scrapie infection. In cultured cells, heparanase treatment or over-expression resulted in a profound decrease in PrPSc. Moreover, disease onset and progression were dramatically delayed in scrapie infected transgenic mice over-expressing heparanase. Together, our results provide direct in vivo evidence for the involvement of intact HS in the pathogenesis of prion disease and the protective role of heparanase both in terms of susceptibility to infection and disease progression.
KW - Heparan sulfate
KW - Heparanase
KW - Prion disease
KW - Scrapie prion protein
KW - Survival time
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=84938741022&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2015.06.170
DO - 10.1016/j.bbrc.2015.06.170
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C2 - 26168721
AN - SCOPUS:84938741022
SN - 0006-291X
VL - 464
SP - 698
EP - 704
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
M1 - 34204
ER -