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-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.
Hafiz
F B
FB
Department of Biochemistry, Cambridge University, Cambridge, CB2 1QW, United Kingdom.
Brown
D R
DR
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005911:Gliosis / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D017628:Microglia / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D017096:Prion Diseases / Q000473:pathology*; D011328:Prions / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D010446:Peptide Fragments; D011328:Prions; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; C082632:prion protein (106-126); D020928:Mitogen-Activated Protein Kinases