NR AEZV
AU Hafiz,F.B.; Brown,D.R.
TI A model for the mechanism of astrogliosis in prion disease
QU Molecular and Cellular Neurosciences 2000 Sep; 16(3): 221-32
PT journal article
AB 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-1 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.
MH Animal; Astrocytes/*pathology; Cell Cycle/drug effects; Cell Division/physiology; Cells, Cultured; Coculture; Gliosis/*etiology/*pathology; Mice; Microglia/physiology; Mitogen-Activated Protein Kinases/metabolism; Peptide Fragments/*pharmacology; Phosphorylation/drug effects; Polymerase Chain Reaction; Prion Diseases/*pathology; Prions/*pharmacology; Receptors, Interleukin-1/metabolism; Receptors, Interleukin-6/metabolism; Signal Transduction/physiology; Support, Non-U.S. Gov't
AD Department of Biochemistry, Cambridge University, Cambridge, CB2 1QW, United Kingdom.
SP englisch
PO USA