Role of galectin-3 in prion infections of the CNS.
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 PrP(Sc)-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.
Mok
Simon W F
SW
Project Neurodegenerative Diseases, Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany.
Riemer
Constanze
C
Madela
Kazimierz
K
Hsu
Daniel K
DK
Liu
Fu-Tong
FT
Gültner
Sandra
S
Heise
Ines
I
Baier
Michael
M
D000818:Animals; D001343:Autophagy; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015996:Survival Rate
D037502:Galectin 3; D052119:Lysosomal-Associated Membrane Protein 2