{"corpus_id":267187758,"paper_sha":"b81d9ca763011d67455b77a2f62f4bbe7dc11e0a","doi":"10.3389/fnagi.2023.1327756","arxiv_id":null,"pmid":38283068,"pmcid":"10811154","mag_id":null,"dblp_id":null,"acl_id":null,"title":"Activated microglia release β−galactosidase that promotes inflammatory neurodegeneration","year":2024,"publication_date":"2024-01-12","venue":"Frontiers in Aging Neuroscience","journal":{"name":"Frontiers in Aging Neuroscience","pages":null,"volume":"15"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":50,"citation_count":6,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":null,"chemicals":null,"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.frontiersin.org/articles/10.3389/fnagi.2023.1327756/pdf?isPublishedV2=False","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/b81d9ca763011d67455b77a2f62f4bbe7dc11e0a","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"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. 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