{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:36:11Z","timestamp":1790890571951,"version":"4.1.0"},"reference-count":241,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The therapeutic potential of functional nutrients has garnered considerable attention for enhancing resilience signaling and counteracting the damage to human health caused by microplastic pollutants. The intricate interactions between microplastics (MPs) and nanoplastics (NPs) and functional nutrients, including polyphenols, flavonoids, phenylpropanoids, phenolic acids, diterpenoids, and triterpenoids, have been shown to improve blood\u2013brain barrier (BBB) homeostasis and brain function by inhibiting oxidative stress, ferroptosis, and inflammation linked to the pathogenesis of metabolic and brain disorders. Interestingly, nutrients exhibit biphasic dose\u2013response effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and stress-resilience proteins at minimum doses, thereby preventing or blocking MP and NP-induced damage. Notably, chronic exposure to environmental pollutants causes aberrant regulation of NFE2L2 gene and related antioxidant signaling, which can exacerbate selective susceptibility to brain insulin resistance under inflammatory conditions. This, in turn, impairs glucose metabolism and facilitates \u03b2-amyloid (A\u03b2) plaque synthesis leading to the onset and progression of Alzheimer\u2019s disease (AD), also known as \u201cType 3 diabetes\u201d. This pathological process triggered by oxidative stress, inflammation, and ferroptosis creates a vicious cycle that ultimately contributes to neuronal damage and loss. The review aims to investigate the therapeutic potential of functional nutrients targeting the Nrf2 pathway and stress resilience proteins to regulate epigenetic alterations, and to explore the underlying molecular mechanisms using innovative in vitro platforms for the development of promising preventive strategies and personalized nutritional interventions to attenuate oxidative stress, ferroptosis, and inflammation, with the goal of ultimately improving clinical outcomes.<\/jats:p>","DOI":"10.3390\/ijms27010169","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:05:22Z","timestamp":1766498722000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Micro- and Nanoplastics and Functional Nutrients in Human Health: Epigenetic Mechanisms and Cellular Resilience Signaling in Brain Insulin Resistance and the Risk of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Cinzia","family":"Lombardo","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Musso","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"},{"name":"Advanced and Innovative Diagnostic Academy (A.I.D.A.) S.r.l., Spin-Off of BRIT Research Center, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-7433","authenticated-orcid":false,"given":"Paolo Giuseppe","family":"Bonacci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-6969","authenticated-orcid":false,"given":"Gabriella","family":"Lupo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-1812","authenticated-orcid":false,"given":"Carmelina Daniela","family":"Anfuso","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3210-1926","authenticated-orcid":false,"given":"Eleonora","family":"Di Fatta","sequence":"additional","affiliation":[{"name":"OASI Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6937-3065","authenticated-orcid":false,"given":"Raffaele","family":"Ferri","sequence":"additional","affiliation":[{"name":"OASI Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-4279","authenticated-orcid":false,"given":"Miroslava","family":"Majz\u00fanov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia"},{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Sienkiewiczova, 84104 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1019-5158","authenticated-orcid":false,"given":"Maria Concetta","family":"Scuto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2377-858X","authenticated-orcid":false,"given":"Angela","family":"Trovato Salinaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.1080\/10408398.2022.2132212","article-title":"Food and Human Safety: The Impact of Microplastics","volume":"64","author":"Knez","year":"2024","journal-title":"Crit. 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