{"doi":"10.15252/msb.20209819","title":"Phosphoproteomics identifies microglial Siglec‐F inflammatory response during neurodegeneration","abstract":"Alzheimer's disease (AD) is characterized by the appearance of amyloid-β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK-p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec-F which was upregulated on a subset of reactive microglia. The human paralog Siglec-8 was also upregulated on microglia in AD. Siglec-F and Siglec-8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV-2 cell line and human stem cell-derived microglia models. Siglec-F overexpression activates an endocytic and pyroptotic inflammatory response in BV-2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine-based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV-2 cells. Collectively, our results point to an important role for mouse Siglec-F and human Siglec-8 in regulating microglial activation during neurodegeneration.","journal":"Molecular Systems Biology","year":2020,"id":59518,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313634,"name":"William T. Ralvenius","orcid":"0000-0002-7279-3252","position":1,"is_corresponding":false},{"id":313635,"name":"Alexi Nott","orcid":"0000-0002-2029-7193","position":2,"is_corresponding":false},{"id":315773,"name":"L. Ashley Watson","orcid":null,"position":3,"is_corresponding":false},{"id":313636,"name":"Felicia H. Rodriguez","orcid":"0000-0002-3136-8831","position":4,"is_corresponding":false},{"id":11610,"name":"Leyla Anne Akay","orcid":"0000-0002-5944-2466","position":5,"is_corresponding":false},{"id":231599,"name":"Brian A. Joughin","orcid":"0000-0003-1022-9450","position":6,"is_corresponding":false},{"id":11598,"name":"Ping-Chieh Pao","orcid":"0000-0001-6788-7185","position":7,"is_corresponding":false},{"id":315774,"name":"Jay Penney","orcid":null,"position":8,"is_corresponding":false},{"id":315775,"name":"Lauren M. LaRocque","orcid":null,"position":9,"is_corresponding":false},{"id":313637,"name":"Diego Mastroeni","orcid":"0000-0001-5878-9372","position":10,"is_corresponding":false},{"id":11618,"name":"Li-Huei Tsai","orcid":"0000-0003-1262-0592","position":11,"is_corresponding":false},{"id":225709,"name":"Forest M. White","orcid":"0000-0002-1545-1651","position":12,"is_corresponding":false},{"id":313633,"name":"Nader Morshed","orcid":"0000-0002-0346-9651","position":0,"is_corresponding":true}],"reference_count":124,"raw_metadata":null,"created_at":"2026-07-18T21:08:26.834549Z","pmid":"33289969","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}