A model for the mechanism of astrogliosis in prion disease

Astrogliosis is a hallmark of prion diseases. Finding ways of inhibiting astrocyte proliferation may be beneficial to treating these diseases. PrP106-126 a peptide fragment of the prion protein induces proliferation of astrocytes. The mechanism of its action was studied in detail. Induction of astrocyte proliferation in culture requires cytokines interleukin-l and interleukin-6 released from microglia in the presence of PrP106-126. However, the increased release of these cytokines is insufficient without direct effects of PrP106-126 on astrocytes. PrP106-126 induces increased progression through the cell cycle to late G1 and enhances the level of both p53 and phosphorylated ERKs in astrocytes. PrP106-126-induced proliferation of astrocytes in culture can be inhibited by antibodies to cytokines or by MEK inhibitors.