{"doi":"10.1101/2025.09.02.673863","title":"DRP1 induces neuroinflammation <i>via</i> transcriptional regulation of NF-ĸB","abstract":"Abstract Neuroinflammation is a major pathogenic mechanism in neurodegenerative diseases. Understanding the regulation of neuroinflammation is critical to therapeutic development. We report here that dynamin related protein 1 (DRP1), well-recognized for its role in mitochondrial fission, is a transcription factor that regulates neuroinflammation. Using multiple inflammatory models, we provide evidence demonstrating that DRP1, when challenged with pro-inflammatory lipopolysaccharides, translocates from the cytosol to the nucleus, then binds to the promoter region of Rela (encoding NF-κB) to activate its gene products and other downstream inflammatory cytokines. Our data also demonstrate the significant role of the proinflammatory lipocalin 2 in the brain. In combination, this study highlights a previously unidentified function of DRP1 in mediating neuroinflammation via the NF-κB-lipocalin 2 axis. Through such mechanisms of DRP1, this study also provides potential therapeutic targets for neurodegenerative diseases and other conditions linked to inflammation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":574326,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1172195,"name":"Rebecca Z. Fan","orcid":"0000-0002-9091-1830","position":1,"is_corresponding":false},{"id":1375097,"name":"Harry Brown","orcid":null,"position":2,"is_corresponding":false},{"id":1172196,"name":"Said S. Salehe","orcid":"0000-0003-2504-9559","position":3,"is_corresponding":false},{"id":1248010,"name":"Ethan Kim Tieu","orcid":"0009-0008-4275-0463","position":4,"is_corresponding":false},{"id":895977,"name":"Kim Tieu","orcid":"0000-0001-6606-4371","position":5,"is_corresponding":false},{"id":290212,"name":"Yanhao Lai","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":"40950203","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":[]}