{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:33:40Z","timestamp":1760060020984,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research (MUR)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Italian Ministry of Health","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Fondazione Romeo ed Enrica Invernizzi","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Inflammasomes regulate the activation of caspases resulting in inflammation; inflammasome activation is dysregulated in Alzheimer\u2019s disease (AD) and plays a role in the pathogenesis of this condition. Glibenclamide, an anti-inflammatory drug, could be an interesting way to down-modulate neuroinflammation. Methods: In this pilot study we verified with ex vivo experiments whether a glibenclamide-loaded nanovector (GNV) could reduce the NLRP3-inflammasome cascade in cells of AD patients. Monocytes isolated from healthy controls (HC) and AD patients were cultured in medium, alone or stimulated with LPS + nigericin in presence\/absence of GNV. ASC-speck positive cells and inflammasome-related genes, proteins, and miRNAs expressions were measured. The polymorphisms of ApoE (Apolipoprotein E), specifically rs7412 and rs429358, as well as those of NLRP3, namely rs35829419, rs10733113, and rs4925663, were also investigated. Results: Results showed that ASC-speck+ cells and Caspase-1, IL-1\u03b2, and IL-18 production was significantly reduced (p &lt; 0.005 in all cases) by GNV in LPS + nigericin-stimulated cells of both AD and HC. Notably, the NLRP3 rs10733113 AG genotype was associated with excessive inflammasome-related gene and protein expression. GNV significantly down-regulates inflammasome activation in primary monocytes, at least at protein levels, and its efficacy seems to partially depend on the presence of the NLRP3 rs10733113 genotype. Conclusions: All together, these results showed that GNV is able to dampen inflammation and NLRP-3 inflammasome activation in an ex vivo monocyte model, suggesting a possible role for GNV in controlling AD-associated neuroinflammation.<\/jats:p>","DOI":"10.3390\/biom15081074","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:19:22Z","timestamp":1753370362000},"page":"1074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Glibenclamide-Loaded Nanovectors Hamper Inflammasome Activation in an Ex Vivo Alzheimer\u2019s Disease Model\u2014A Novel Potential Therapy for Neuroinflammation: A Pilot Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3181-9505","authenticated-orcid":false,"given":"Francesca","family":"La Rosa","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6214-0645","authenticated-orcid":false,"given":"Simone","family":"Agostini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-1697","authenticated-orcid":false,"given":"Elisabetta","family":"Bolognesi","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Marventano","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-3623","authenticated-orcid":false,"given":"Roberta","family":"Mancuso","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Piancone","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro Davide","family":"Trimarchi","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Navarro","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6336-2648","authenticated-orcid":false,"given":"Federica","family":"Rossetto","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Amenta","sequence":"additional","affiliation":[{"name":"Chemistry Department, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-7344","authenticated-orcid":false,"given":"Pierfausto","family":"Seneci","sequence":"additional","affiliation":[{"name":"Chemistry Department, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-9468","authenticated-orcid":false,"given":"Silvia","family":"Sesana","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, 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