{"doi":"10.1126/sciadv.abo4662","title":"Neurons burdened by DNA double-strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration","abstract":"DNA double-strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize DSB-bearing neurons from the CK-p25 mouse model of neurodegeneration using single-nucleus, bulk, and spatial transcriptomic techniques. DSB-bearing neurons enter a late-stage DNA damage response marked by nuclear factor κB (NFκB)-activated senescent and antiviral immune pathways. In humans, Alzheimer's disease pathology is closely associated with immune activation in excitatory neurons. Spatial transcriptomics reveal that regions of CK-p25 brain tissue dense with DSB-bearing neurons harbor signatures of inflammatory microglia, which is ameliorated by NFκB knockdown in neurons. Inhibition of NFκB in DSB-bearing neurons also reduces microglia activation in organotypic mouse brain slice culture. In conclusion, DSBs activate immune pathways in neurons, which in turn adopt a senescence-associated secretory phenotype to elicit microglia activation. These findings highlight a previously unidentified role for neurons in the mechanism of disease-associated neuroinflammation.","journal":"Science Advances","year":2022,"id":1318,"datarank":2.318463522165858,"base_score":4.418840607796598,"endowment":4.418840607796598,"self_citation_contribution":0.6628260911694899,"citation_network_contribution":1.6556374309963682,"self_endowment_contribution":0.6628260911694899,"citer_contribution":1.6556374309963682,"corpus_percentile":null,"corpus_rank":null,"citation_count":82,"citer_count":69,"citers_with_citation_signal":60,"citers_with_endowment":60,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0475,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-09-30","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":4960,"name":"Carles B. Adsera","orcid":"0000-0001-9212-856X","position":1,"is_corresponding":false},{"id":5683,"name":"Eloi Schmauch","orcid":"0000-0002-2123-8777","position":2,"is_corresponding":false},{"id":1204,"name":"José Dávila-Velderrain","orcid":"0000-0003-0271-6267","position":3,"is_corresponding":false},{"id":11603,"name":"Matheus B. Victor","orcid":"0000-0003-4364-4028","position":4,"is_corresponding":false},{"id":16445,"name":"Vishnu Dileep","orcid":"0000-0001-9181-2191","position":5,"is_corresponding":false},{"id":16446,"name":"P. Lorenzo Bozzelli","orcid":"0000-0002-3760-521X","position":6,"is_corresponding":false},{"id":16447,"name":"Qiao Su","orcid":"0000-0002-7882-6182","position":7,"is_corresponding":false},{"id":16448,"name":"Jemmie D. Cheng","orcid":null,"position":8,"is_corresponding":false},{"id":16449,"name":"Audrey Lee","orcid":"0000-0002-4830-5781","position":9,"is_corresponding":false},{"id":16451,"name":"Andreas R. Pfenning","orcid":"0000-0002-3447-9801","position":11,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":12,"is_corresponding":false},{"id":11618,"name":"Li-Huei Tsai","orcid":"0000-0003-1262-0592","position":13,"is_corresponding":false},{"id":71429,"name":"Gloria Suella Menchaca","orcid":null,"position":15,"is_corresponding":false},{"id":16444,"name":"Gwyneth M. Welch","orcid":"0000-0003-1635-1190","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}