AUTHOR=Kitchener Emily J. A. , Dundee Jacob M. , Brown Guy C. TITLE=Activated microglia release β−galactosidase that promotes inflammatory neurodegeneration JOURNAL=Frontiers in Aging Neuroscience VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1327756 DOI=10.3389/fnagi.2023.1327756 ISSN=1663-4365 ABSTRACT=

Beta (β)-galactosidase is a lysosomal enzyme that removes terminal galactose residues from glycolipids and glycoproteins. It is upregulated in, and used as a marker for, senescent cells. Microglia are brain macrophages implicated in neurodegeneration, and can upregulate β-galactosidase when senescent. We find that inflammatory activation of microglia induced by lipopolysaccharide results in translocation of β-galactosidase to the cell surface and release into the medium. Similarly, microglia in aged mouse brains appear to have more β-galactosidase on their surface. Addition of β-galactosidase to neuronal-glial cultures causes microglial activation and neuronal loss mediated by microglia. Inhibition of β-galactosidase in neuronal-glial cultures reduces inflammation and neuronal loss induced by lipopolysaccharide. Thus, activated microglia release β-galactosidase that promotes microglial-mediated neurodegeneration which is prevented by inhibition of β-galactosidase.