{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:45:00Z","timestamp":1790628300002,"version":"4.1.0"},"reference-count":147,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007254","name":"Creighton University","doi-asserted-by":"crossref","award":["LB595"],"award-info":[{"award-number":["LB595"]}],"id":[{"id":"10.13039\/100007254","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007254","name":"Creighton University","doi-asserted-by":"crossref","award":["LB692"],"award-info":[{"award-number":["LB692"]}],"id":[{"id":"10.13039\/100007254","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cognitive Neuroscience of Development and Aging (CoNDA) Center","award":["3P20GM130447-04S1"],"award-info":[{"award-number":["3P20GM130447-04S1"]}]},{"name":"NIGMS-Creighton University CoBRE Program grant","award":["5P20GM139762-02"],"award-info":[{"award-number":["5P20GM139762-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Triggering receptor expressed on myeloid cells-1 (TREM-1), a member of the immunoglobulin superfamily, plays a crucial role in amplifying inflammatory responses, thereby contributing to the pathogenesis and progression of various inflammatory diseases. This review presents a comprehensive analysis of the current understanding of TREM-1 signaling and its dysregulation in disease pathology. Additionally, it explores the prognostic significance of TREM-1 across a spectrum of conditions. Targeting TREM-1 signaling represents a promising therapeutic approach for managing a wide range of diseases, including cancer, neurodegenerative disorders, cardiovascular diseases, and other inflammation-driven conditions. Previous reviews on TREM-1 have largely focused on its immunological role across diverse disease conditions and selective peptide-based inhibitors targeting its signaling pathway. However, recent discoveries have identified small-molecule modulators of TREM-1 that offer new opportunities for therapeutic intervention. Incorporating these findings would provide a more comprehensive and updated perspective on TREM-1 biology, particularly regarding its molecular regulation, drug-target potential, and translational relevance in inflammatory and immune-mediated disorders. Advances in this field are expected to be driven by structure-based drug design, particularly in the development of TREM-1 inhibitors. However, further research is needed to elucidate the predictive value of TREM-1 alterations and to evaluate them in prospective human studies prior to clinical decision-making.<\/jats:p>","DOI":"10.3390\/ijms262110386","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:51:42Z","timestamp":1761526302000},"page":"10386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) in Inflammation and Disease: Mechanisms, Therapeutic Potential, and Future Directions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2715-6470","authenticated-orcid":false,"given":"Neerja","family":"Trivedi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7171-8648","authenticated-orcid":false,"given":"Jitendra D.","family":"Bhosale","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali P.","family":"Suryawanshi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Bharati Vidyapeeth Deemed University Medical College, Pune 411043, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4565-2151","authenticated-orcid":false,"given":"Prerna","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Abel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-5574","authenticated-orcid":false,"given":"Gopal P.","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4991","DOI":"10.4049\/jimmunol.164.10.4991","article-title":"Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes","volume":"164","author":"Bouchon","year":"2000","journal-title":"J. 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