NR AXEU
AU Mok,S.W.F.; Riemer,C.; Madela,K.; Hsu,D.K.; Liu,F.T.; Gultner,S.; Heise,I.; Baier,M.
TI Role of galectin-3 in prion infections of the CNS
QU Biochemical and Biophysical Research Communications 2007 Aug 3; 359(3): 672-8
PT journal article; research support, non-u.s. gov't
AB Galectin-3 is a multi-functional protein and participates in mediating inflammatory reactions. The pronounced overexpression of galectin-3 in prion-infected brain tissue prompted us to study the role of this protein in a murine prion model. Immunofluorescence double-labelling identified microglia as the major cell type expressing galectin-3. Ablation of galectin-3 did not affect PrPsc-deposition and development of gliosis. However, galectin-3(-/-)-mice showed prolonged survival times upon intracerebral and peripheral scrapie infections. Moreover, protein levels of the lysosomal activation marker LAMP-2 were markedly reduced in prion-infected galectin-3(-/-)-mice suggesting a role of galectin-3 in regulation of lysosomal functions. Lower mRNA levels of Beclin-1 and Atg5 in prion-infected wild-type and galectin-3(-/-)-mice indicated an impairment of autophagy although autophagosome formation was unchanged. The results point towards a detrimental role of galectin-3 in prion infections of the CNS and suggest that endo-/lysosomal dysfunction in combination with reduced autophagy may contribute to disease development.
IN Die Expression des Gens Galectin-3 kann die Inkubationszeit von Prionkrankheiten beeinflussen.
MH Animals; Autophagy; Galectin 3/deficiency/genetics/*metabolism; Gene Expression Regulation; Immunohistochemistry; Lysosomal-Associated Membrane Protein 2/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Prion Diseases/genetics/*metabolism/*pathology; Survival Rate
AD Project Neurodegenerative Diseases, Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany.
SP englisch
PO USA