{"doi":"10.1016/j.jacig.2023.100082","title":"EP2 inhibition restores myeloid metabolism and reverses cognitive decline","abstract":"Nonsteroidal anti-inflammatory drugs alleviate pain and inflammation by inhibiting the cyclooxygenase pathway. This pathway has various downstream effects, some of which are beneficial. Prostaglandin E2 is a key downstream product in the cyclooxygenase pathway that modulates inflammation. A correlation between aging and increased expression of the prostaglandin E2 receptor, EP2, has been associated with inflammatory processes, cognitive aging, angiogenesis, and tumorigenesis. Therefore, inhibition of EP2 could lead to therapeutic effects and be more selective than inhibiting cyclooxygenase-2. Studies suggest that inhibition of EP2 restores age-associated spatial memory deficits and synaptic proteins and impairs tumorigenesis. The data indicate that EP2 signaling is important in myeloid cell metabolism and support its candidacy as a therapeutic target. Nonsteroidal anti-inflammatory drugs alleviate pain and inflammation by inhibiting the cyclooxygenase pathway. This pathway has various downstream effects, some of which are beneficial. Prostaglandin E2 is a key downstream product in the cyclooxygenase pathway that modulates inflammation. A correlation between aging and increased expression of the prostaglandin E2 receptor, EP2, has been associated with inflammatory processes, cognitive aging, angiogenesis, and tumorigenesis. Therefore, inhibition of EP2 could lead to therapeutic effects and be more selective than inhibiting cyclooxygenase-2. Studies suggest that inhibition of EP2 restores age-associated spatial memory deficits and synaptic proteins and impairs tumorigenesis. The data indicate that EP2 signaling is important in myeloid cell metabolism and support its candidacy as a therapeutic target. The cyclooxygenase (COX) pathway synthesizes prostanoids from the substrate arachidonic acid. These include prostaglandins PGH2, PGE2, PGD2, PGF2α, prostacyclin PGI2, and thromboxane TXA2. Studies suggest a positive correlation between the administration of COX-2 inhibitors and the reduction in certain cancers, cancer-related mortality, and neuroinflammation.1Jiang J. Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection.Trends Pharmacol Sci. 2013; 34: 413-423Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Prostaglandin E2 (PGE2) is a product of the COX-2 pathway and has been implicated in the process of inflammation, cognitive aging, angiogenesis, and tumorigenesis.1Jiang J. Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection.Trends Pharmacol Sci. 2013; 34: 413-423Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Prostaglandin signaling occurs through 4 G-protein–coupled receptors: EP1, 2, 3, and 4.2Breyer R.M. Bagdassarian C.K. Myers S.A. Breyer M.D. Prostanoid receptors: subtypes and signaling.Annu Rev Pharmacol Toxicol. 2001; 41: 661-690Crossref PubMed Scopus (854) Google Scholar PGE2 signaling of the EP2 receptor leads to potentially beneficial or harmful effects that vary with the signaling components and the type of stimulus.1Jiang J. Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection.Trends Pharmacol Sci. 2013; 34: 413-423Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar PGE2-EP2 signaling may serve as a valuable therapeutic target given its presence and impact in inflammation, neurodegeneration, cytoprotection, tumorigenesis, and angiogenesis. It is crucial to recognize the components involved in PGE2-EP2 signaling to better understand the various downstream effects of this pathway. When stimulated by PGE2, the EP2 receptor mediates either a G protein–dependent response or a G protein–independent response. In the G protein–dependent pathway, EP2 functions as a stimulatory G (Gs) protein–coupled receptor that leads to adenyl cyclase activation and increased levels of cytoplasmic cyclic ad","journal":"Journal of Allergy and Clinical Immunology Global","year":2023,"id":367864,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1125455,"name":"Samuel Camilli","orcid":"0000-0001-7400-4299","position":1,"is_corresponding":false},{"id":1125837,"name":"Francisco Pascual","orcid":null,"position":2,"is_corresponding":false},{"id":502549,"name":"Richard F. Lockey","orcid":"0000-0003-0279-8661","position":3,"is_corresponding":false},{"id":1125456,"name":"Narasaiah Kolliputi","orcid":"0000-0002-1922-3533","position":4,"is_corresponding":false},{"id":1125454,"name":"Ryan Lushington","orcid":"0000-0001-5366-4319","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:15:16.306414Z","pmid":"37780795","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":[]}