| Autor: |
Engelstein, R., Ovadia, H., Gabizon, R. |
| Předmět: |
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| Zdroj: |
European Journal of Neurology; Aug2007, Vol. 14 Issue 8, p877-884, 8p, 3 Black and White Photographs, 1 Graph |
| Abstrakt: |
The hallmark of prion disease-induced neurodegeneration is the accumulation of PrPSc, a misfolded form of PrPC. In addition, several lines of evidence indicate a role for the immune system and, in particular, inflammation in prion disease pathogenesis. In this work, we tested whether Copaxone, an immunomodulatory agent currently used for the treatment of multiple sclerosis, can affect prion disease manifestation in scrapie-infected hamsters. We show here that Copaxone exerted no effect on prion disease incubation time when treatment commenced 2 weeks after i.p. prion infection. However, when Copaxone was mixed with the initial prion inoculum or administered to hamsters weekly starting on the day of infection, prion disease incubation time was prolonged by 30 days. This suggests that Copaxone may affect the initial infection process. In vitro experiments indicate that Copaxone significantly reduced PrPSc binding to both Chinese hamster ovary (CHO) cells and heparin beads and also binds to heparin by itself. Interestingly, Copaxone also abolished PrPSc accumulation in scrapie-infected cells. We propose that Copaxone delays prion infection by competing with the PrPSc–glycosaminoglycans interaction. Whether the immunomodulating activity of Copaxone is related to its heparin binding and anti-prion properties remains to be established. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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