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Several natural compounds have been investigated, particularly resveratrol (RSV), which exhibits antioxidant and anti-inflammatory properties. However, its unfavorable pharmacokinetic profile limits its therapeutic application, making nanoencapsulation a promising strategy. This study evaluated the protective effects of resveratrol-loaded polymeric nanoparticles (NP RSV) and the involvement of the Keap1\/NRF2\/ARE pathway in a rotenone (ROT)-induced PD-like model in vitro. PC12 neuronal cells and astrocytes were pretreated with NP RSV, RSV, and dopamine for 1\u00a0h, followed by ROT exposure for 24\u00a0h. Cell viability was assessed by MTT, while cell death profile, reactive oxygen species production, and mitochondrial transmembrane potential (\u0394\u03a8m) were evaluated by flow cytometry. Morphological changes were evaluated by optical microscopy. Gene expression of\n                    <jats:italic>NRF2<\/jats:italic>\n                    and heme oxygenase-1 (HMOX-1) was assessed by RT-qPCR. Pretreatment with NP RSV significantly protected cells by preserving viability, reducing reactive oxygen species, maintaining mitochondrial function, and decreasing apoptosis. Morphological analyses corroborated these results. Furthermore, NP RSV modulated ROT-induced\n                    <jats:italic>NRF2<\/jats:italic>\n                    and\n                    <jats:italic>HMOX-1<\/jats:italic>\n                    expression, suggesting involvement of the Keap1\/NRF2\/ARE pathway.\n                  <\/jats:p>","DOI":"10.1007\/s11064-026-04749-z","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:11:15Z","timestamp":1776075075000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resveratrol-Loaded Polymeric Nanoparticles Protect Against Rotenone-Induced Parkinsonian-Like Cellular Damage In Vitro: Association with NRF2\/HMOX-1 Expression Changes"],"prefix":"10.1007","volume":"51","author":[{"given":"Izabell Maria Martins","family":"Teixeira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Ribeiro","family":"Duque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mac Dionys Rodrigues","family":"da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus Edson","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus Oliveira","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nia Gabriella","family":"de Souza Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Mendes","family":"Bezerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Vit\u00f3ria Frota","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Maria Lima","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Antonio","family":"de Freitas Clementino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josimar Oliveira","family":"Eloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon R\u00f3seo Paula Pessoa Bezerra","family":"de Menenzes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Maria Costa","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago Lima","family":"Sampaio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"4749_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","volume":"403","author":"HR Morris","year":"2024","unstructured":"Morris HR, Spillantini MG, Sue CM, Williams-Gray CH (2024) The pathogenesis of Parkinson\u2019s disease. 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