{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:21:03Z","timestamp":1774084863372,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2022XF7XZF"],"award-info":[{"award-number":["2022XF7XZF"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of 11\u03b2-HSD1 in Alzheimer\u2019s disease (AD) has garnered significant attention due to its involvement in glucocorticoid metabolism, neuroinflammation, and cognitive decline. This review explores the current understanding of 11\u03b2-HSD1 in AD, examining genetic, preclinical, and clinical research. Genetic studies have identified 11\u03b2-HSD1 polymorphisms that may influence AD risk, although findings remain inconsistent. Mechanistically, 11\u03b2-HSD1 promotes neurodegeneration through the dysregulation of glucocorticoid activity, contributing to hippocampal atrophy, amyloid plaque formation, and tau pathology. Preclinical studies have shown that 11\u03b2-HSD1 inhibitors offer neuroprotective effects, including enhanced cognitive function, reduced inflammation, and improved mitochondrial activity. However, clinical trials, including those involving ABT-384 and Xanamem, have produced mixed results, with no substantial cognitive improvements despite effective enzyme inhibition. These inconsistencies highlight the complexity of AD and the challenges in translating preclinical findings into clinical outcomes. Moreover, while 11\u03b2-HSD1 inhibition holds therapeutic potential, other strategies targeting neuroinflammation, autophagy, and glucocorticoid signaling are also being explored. Ongoing research is focusing on optimizing 11\u03b2-HSD1 inhibitors, identifying biomarkers for patient selection, and investigating combination therapies to enhance treatment efficacy. Ultimately, 11\u03b2-HSD1\u2019s role in AD presents a promising therapeutic target, but further studies are required to fully understand its potential in managing the disease.<\/jats:p>","DOI":"10.3390\/ijms26031357","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T04:47:31Z","timestamp":1738817251000},"page":"1357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of 11\u03b2-Hydroxysteroid Dehydrogenase and Mineralocorticoid Receptor on Alzheimer\u2019s Disease Onset: A Systematic Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Mariangela","family":"Di Vincenzo","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Sciences\u2014Histology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences\u2014Histology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genny","family":"Schiappa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences\u2014Histology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Campanati","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences\u2014Dermatological Clinic, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Del Vescovo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences\u2014Histology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7608-5589","authenticated-orcid":false,"given":"Silvia","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health\u2014Pharmacology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-0725","authenticated-orcid":false,"given":"Patrizia","family":"Ambrogini","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Arnaldi","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) \u201cG. D\u2019Alessandro\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-3693","authenticated-orcid":false,"given":"Monia","family":"Orciani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences\u2014Histology, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Preziuso, A., Piccirillo, S., Cerqueni, G., Serfilippi, T., Terenzi, V., Vinciguerra, A., Orciani, M., Amoroso, S., Magi, S., and Lariccia, V. (2023). Exploring the Role of NCX1 and NCX3 in an In Vitro Model of Metabolism Impairment: Potential Neuroprotective Targets for Alzheimer\u2019s Disease. 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