Sialidase neu4 deficiency is associated with neuroinflammation in mice.

Autor: Timur ZK; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Urla, Izmir, Turkey., Inci OK; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Urla, Izmir, Turkey., Demir SA; Izmir Institute of Technology, IYTEDEHAM, Urla, İzmir, Turkey., Seyrantepe V; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Urla, Izmir, Turkey. volkanseyrantepe@iyte.edu.tr.; Izmir Institute of Technology, IYTEDEHAM, Urla, İzmir, Turkey. volkanseyrantepe@iyte.edu.tr.
Jazyk: angličtina
Zdroj: Glycoconjugate journal [Glycoconj J] 2021 Dec; Vol. 38 (6), pp. 649-667. Date of Electronic Publication: 2021 Oct 23.
DOI: 10.1007/s10719-021-10017-9
Abstrakt: Sialidases catalyze the removal of sialic acid residues from glycoproteins, oligosaccharides, and sialylated glycolipids. Sialidase Neu4 is in the lysosome and has broad substrate specificity. Previously generated Neu4-/- mice were viable, fertile and lacked gross morphological abnormalities, but displayed a marked vacuolization and lysosomal storage in lung and spleen cells. In addition, we showed that there is an increased level of GD1a ganglioside and a markedly decreased level of GM1 ganglioside in the brain of Neu4-/- mice. In this study, we further explored whether sialidase Neu4 deficiency causes neuroinflammation. We demostrated that elevated level of GD1a and GT1b is associated with an increased level of LAMP1-positive lysosomal vesicles and Tunel-positive neurons correlated with alterations in the expression of cytokines and chemokines in adult Neu4-/- mice. Astrogliosis and microgliosis were also significantly enhanced in the hippocampus, and cerebellum. These changes in brain immunity were accompanied by motor impairment in these mice. Our results indicate that sialidase Neu4 is a novel mediator of an inflammatory response in the mouse brain due to the altered catabolism of gangliosides.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: