A neurotoxic prion protein fragment enhances proliferation of microglia but not astrocytes in culture.

作者: David R. Brown , Bernhard Schmidt , Hans A. Kretzschmar

DOI: 10.1002/(SICI)1098-1136(199609)18:1<59::AID-GLIA6>3.0.CO;2-Z

关键词: Central nervous systemScrapieGliosisBiologyNeurogliaGene isoformCell biologyMicrogliaImmunologyNeurodegenerationAstrocyte

摘要: The scrapie isoform of the prion protein (PrP Sc ) induces pathological changes in central nervous system including neurodegeneration and gliosis. A synthetic (PrP) peptide corresponding to amino acid residues 106-126 has been shown be toxic neurons that express PrPC, cellular PrP. Here we show mixed glial cultures PrP106-126 astroglial proliferation is dependent on PrP c expression. In purified subtypes only microglia proliferated response PrP106-126. This effect was independent Destruction by L-leucine methyl ester (LLME) treatment abolished enhanced caused proliferative can restored co-culturing LLME-treated astrocytes with microglia. Microglia therefore seem mediate exerted astrocytes.

参考文章(46)
D.R. Borchelt, A Taraboulos, S.B. Prusiner, Evidence for synthesis of scrapie prion proteins in the endocytic pathway. Journal of Biological Chemistry. ,vol. 267, pp. 16188- 16199 ,(1992) , 10.1016/S0021-9258(18)41985-0
H. A. Kretzschmar, S. B. Prusiner, S. J. DeArmond, L. E. Stowring, Scrapie prion proteins are synthesized in neurons. American Journal of Pathology. ,vol. 122, pp. 1- 5 ,(1986)
L. De Gioia, C. Selvaggini, E. Ghibaudi, L. Diomede, O. Bugiani, G. Forloni, F. Tagliavini, M. Salmona, Conformational polymorphism of the amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein. Journal of Biological Chemistry. ,vol. 269, pp. 7859- 7862 ,(1994) , 10.1016/S0021-9258(17)37129-6
D Giulian, TJ Baker, Characterization of ameboid microglia isolated from developing mammalian brain The Journal of Neuroscience. ,vol. 6, pp. 2163- 2178 ,(1986) , 10.1523/JNEUROSCI.06-08-02163.1986
J Manson, J Hope, M H Kaufman, V Thomson, J D West, P McBride, The prion protein gene: a role in mouse embryogenesis? Development. ,vol. 115, pp. 117- 122 ,(1992)
Gianluigi Forloni, Nadia Angeretti, Roberto Chiesa, Enrico Monzani, Mario Salmona, Orso Bugiani, Fabrizio Tagliavini, Neurotoxicity of a prion protein fragment Nature. ,vol. 362, pp. 543- 546 ,(1993) , 10.1038/362543A0
Gerald W. Both, Yasuhiro Furuichi, S. Muthukrishnan, A.J. Shatkin, Ribosome binding to reovirus mRNA in protein synthesis requires 5' terminal 7-methylguanosine. Cell. ,vol. 6, pp. 185- 195 ,(1975) , 10.1016/0092-8674(75)90009-4
Markus Moser, Raymond J Colello, Uwe Pott, Bruno Oesch, Developmental expression of the prion protein gene in glial cells Neuron. ,vol. 14, pp. 509- 517 ,(1995) , 10.1016/0896-6273(95)90307-0
F. Tagliavini, F. Prelli, L. Verga, G. Giaccone, R. Sarma, P. Gorevic, B. Ghetti, F. Passerini, E. Ghibaudi, G. Forloni, Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 9678- 9682 ,(1993) , 10.1073/PNAS.90.20.9678