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Cortistatin (CST), an endogenous neuropeptide structurally related to somatostatin, has emerged as a multifunctional regulator of neuroimmune and immunometabolic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This scoping review was conducted in accordance with PRISMA-ScR guidelines and maps and synthesizes preclinical evidence on the biological roles and therapeutic potential of CST across experimental disease models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A comprehensive literature search identified 31 preclinical studies published between 2006 and 2025 that evaluated CST administration or cortistatin deficiency. Despite substantial heterogeneity in disease models, including neurodegenerative, autoimmune, cardiovascular, fibrotic, and musculoskeletal conditions, CST consistently demonstrated protective effects. Across studies, CST reduced pro-inflammatory cytokine production, attenuated tissue damage, and improved functional outcomes and survival. Mechanistically, CST modulated key inflammatory pathways such as NF-\u03baB signaling and NLRP3 inflammasome activation, suppressed Th1 and Th17 responses, and promoted regulatory T cell expansion through interactions with somatostatin receptors, GHSR1a, and MrgX2. Emerging translational strategies, including peptide analogues, protease-activated prodrugs, and nanoparticle-based delivery systems, have improved pharmacokinetic stability and therapeutic efficacy in experimental models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these findings establish cortistatin as a consistent endogenous regulator of neuroimmune responses across diverse experimental conditions, highlighting its potential as a promising therapeutic target for immunomodulation in complex inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10787-026-02319-x","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:58:45Z","timestamp":1782889125000},"page":"5031-5046","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cortistatin as a pleiotropic regulator of neuroimmune and inflammatory pathways in experimental disease: a scoping review of preclinical evidence"],"prefix":"10.1007","volume":"34","author":[{"given":"Marcelo Eduardo","family":"Cardozo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Victor Cardoso","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Lacerda","family":"Bueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Toshio","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Laura Grossi","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3193-8603","authenticated-orcid":false,"given":"Cristiane Alves da Silva","family":"Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"2319_CR1","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.4103\/ijo.IJO_290_20","volume":"68","author":"M Balbaba","year":"2020","unstructured":"Balbaba M, Dal A, \u00c7olako\u01e7lu N, Bulmu\u015f \u00d6, Ula\u015f F, Yildirim H et al (2020) Anti-inflammatory effect of cortistatin in rat endotoxin-induced uveitis model. 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