{"doi":"10.1038/s41598-024-65248-1","title":"The impact of astrocytic NF-κB on healthy and Alzheimer’s disease brains","abstract":"Abstract Astrocytes play a role in healthy cognitive function and Alzheimer’s disease (AD). The transcriptional factor nuclear factor-κB (NF-κB) drives astrocyte diversity, but the mechanisms are not fully understood. By combining studies in human brains and animal models and selectively manipulating NF-κB function in astrocytes, we deepened the understanding of the role of astrocytic NF-κB in brain health and AD. In silico analysis of bulk and cell-specific transcriptomic data revealed the association of NF-κB and astrocytes in AD. Confocal studies validated the higher level of p50 NF-κB and phosphorylated-p65 NF-κB in glial fibrillary acidic protein (GFAP) + -astrocytes in AD versus non-AD subjects. In the healthy mouse brain, chronic activation of astrocytic NF-κB disturbed the proteomic milieu, causing a loss of mitochondrial-associated proteins and the rise of inflammatory-related proteins. Sustained NF-κB signaling also led to microglial reactivity, production of pro-inflammatory mediators, and buildup of senescence-related protein p16 INK4A in neurons. However, in an AD mouse model, NF-κB inhibition accelerated β-amyloid and tau accumulation. Molecular biology studies revealed that astrocytic NF-κB activation drives the increase in GFAP and inflammatory proteins and aquaporin-4, a glymphatic system protein that assists in mitigating AD. Our investigation uncovered fundamental mechanisms by which NF-κB enables astrocytes' neuroprotective and neurotoxic responses in the brain.","journal":"Scientific Reports","year":2024,"id":418274,"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":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254615,"name":"Judith Camats‐Perna","orcid":"0000-0003-0696-1059","position":1,"is_corresponding":false},{"id":948168,"name":"Estella A. Newcombe","orcid":"0000-0001-6132-6168","position":2,"is_corresponding":false},{"id":781269,"name":"Tessa Onraet","orcid":"0000-0002-9273-2908","position":3,"is_corresponding":false},{"id":1205773,"name":"Daniel Campbell","orcid":"0009-0006-7998-1690","position":4,"is_corresponding":false},{"id":1206618,"name":"Josiah T. Sucic","orcid":null,"position":5,"is_corresponding":false},{"id":315606,"name":"Alessandra Cadete Martini","orcid":"0000-0002-8447-6756","position":6,"is_corresponding":false},{"id":315607,"name":"Stefânia Forner","orcid":"0000-0001-7977-4866","position":7,"is_corresponding":false},{"id":808173,"name":"Mehdi Mirzaei","orcid":"0000-0001-8727-4984","position":8,"is_corresponding":false},{"id":308304,"name":"Wayne W. Poon","orcid":"0000-0003-0625-3968","position":9,"is_corresponding":false},{"id":315609,"name":"Frank M. LaFerla","orcid":"0000-0003-2324-6911","position":10,"is_corresponding":false},{"id":254616,"name":"Rodrigo Medeiros","orcid":"0000-0002-9399-7852","position":11,"is_corresponding":false},{"id":948167,"name":"Tee Jong Huat","orcid":"0000-0003-3436-8148","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38906984","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":[]}