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Pterostilbene (PTR) is a natural stilbene with reported antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed to prioritize putative PTR-associated targets and biological processes potentially relevant to shared neurodegenerative mechanisms. Methods: An integrative in silico workflow combining network pharmacology, protein\u2013protein interaction (PPI) analysis, GO Biological Process (GO BP) enrichment, molecular docking, and molecular dynamics (MD) simulations was applied. GO BP terms were filtered, focused on neurodegeneration- and neuroprotection-related processes, and subjected to REVIGO-based redundancy reduction. Selected targets were further evaluated by docking and 500 ns MD simulations. Results: A total of 181, 165, 128, and 109 shared PTR\u2013disease targets were identified for AD, PD, HD, and ALS, respectively. Redundancy-reduced GO BP analysis indicated associations with neuroinflammation, oxidative stress and reactive oxygen species-related responses, programmed cell death, MAPK\/ERK- and PI3K\/AKT-related signaling, ion and calcium transport, and lipid-, steroid-, or hormone-associated regulation. PPI topology prioritized SRC, ESR1, and HSP90AA1 as recurrent hub\u2013bottleneck proteins, whereas MD-based structural interpretation focused on ESR1 and HSP90AA1. MD analyses indicated stable PTR interactions with both proteins, with ESR1 showing the most favorable predicted interaction profile. Conclusions: These findings suggest that PTR may interact with shared neurodegeneration-relevant molecular systems, particularly through ESR1- and HSP90AA1-associated mechanisms. However, the results are exclusively computational and should be interpreted as hypothesis-generating, requiring further experimental validation.<\/jats:p>","DOI":"10.3390\/ph19071053","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:27:23Z","timestamp":1783520843000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Network Pharmacology and Molecular Docking Analysis Reveals the Multitarget Mechanisms of Pterostilbene in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-6413","authenticated-orcid":false,"given":"Natalia","family":"Rosiak","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-8395","authenticated-orcid":false,"given":"Filip","family":"Stojceski","sequence":"additional","affiliation":[{"name":"SUPSI, IDSIA-Dalle Molle Institute for Artificial Intelligence (USI-SUPSI), Polo Universitario Lugano-Campus Est, Via la Santa 1, CH-6962 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Maroni","sequence":"additional","affiliation":[{"name":"SUPSI, IDSIA-Dalle Molle Institute for Artificial Intelligence (USI-SUPSI), Polo Universitario Lugano-Campus Est, Via la Santa 1, CH-6962 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Piontek","sequence":"additional","affiliation":[{"name":"Poznan Supercoputing and Networking Center, Jana Paw\u0142a II 10 Street, 61-139 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-5419","authenticated-orcid":false,"given":"Judyta","family":"Cielecka-Piontek","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1021\/acs.molpharmaceut.7b00545","article-title":"Bioavailability of polyphenols and flavonoids in the era of precision medicine","volume":"14","author":"Hu","year":"2017","journal-title":"Mol. 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