{"doi":"10.1016/j.bbi.2024.02.023","title":"A critical role for Macrophage-derived Cysteinyl-Leukotrienes in HIV-1 induced neuronal injury","abstract":"Macrophages (MΦ) infected with human immunodeficiency virus (HIV)-1 or activated by its envelope protein gp120 exert neurotoxicity. We found previously that signaling via p38 mitogen-activated protein kinase (p38 MAPK) is essential to the neurotoxicity of HIVgp120-stimulated MΦ. However, the associated downstream pathways remained elusive. Here we show that cysteinyl-leukotrienes (CysLT) released by HIV-infected or HIVgp120 stimulated MΦ downstream of p38 MAPK critically contribute to neurotoxicity. SiRNA-mediated or pharmacological inhibition of p38 MAPK deprives MΦ of CysLT synthase (LTC4S) and, pharmacological inhibition of the cysteinyl-leukotriene receptor 1 (CYSLTR1) protects cerebrocortical neurons against toxicity of both gp120-stimulated and HIV-infected MΦ. Components of the CysLT pathway are differentially regulated in brains of HIV-infected individuals and a transgenic mouse model of NeuroHIV (HIVgp120tg). Moreover, genetic ablation of LTC4S or CysLTR1 prevents neuronal damage and impairment of spatial memory in HIVgp120tg mice. Altogether, our findings suggest a novel critical role for cysteinyl-leukotrienes in HIV-associated brain injury.","journal":"Brain Behavior and Immunity","year":2024,"id":478459,"datarank":0.18345518378535278,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.018663340485136324,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.018663340485136324,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"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":98606,"name":"Kathryn E. Medders","orcid":null,"position":1,"is_corresponding":false},{"id":876665,"name":"Ana B. Sánchez","orcid":null,"position":2,"is_corresponding":false},{"id":366783,"name":"Rohan Shah","orcid":"0000-0003-4796-0394","position":3,"is_corresponding":false},{"id":1317589,"name":"Cyrus M. de Rozieres","orcid":null,"position":4,"is_corresponding":false},{"id":366782,"name":"Daniel Ojeda-Juárez","orcid":"0000-0002-0722-2509","position":5,"is_corresponding":false},{"id":368029,"name":"Ricky Maung","orcid":null,"position":6,"is_corresponding":false},{"id":388356,"name":"Roy Williams","orcid":"0000-0001-6735-6990","position":7,"is_corresponding":false},{"id":484058,"name":"Benjamin B. Gelman","orcid":null,"position":8,"is_corresponding":false},{"id":484059,"name":"Bas Baaten","orcid":null,"position":9,"is_corresponding":false},{"id":262442,"name":"Amanda J. Roberts","orcid":"0000-0002-4044-8884","position":10,"is_corresponding":false},{"id":366784,"name":"Marcus Kaul","orcid":"0000-0003-3202-670X","position":11,"is_corresponding":false},{"id":934511,"name":"Nina Y. Yuan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:46.330532Z","pmid":"38423397","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":[]}