{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:06:54Z","timestamp":1779368814839,"version":"3.53.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Herein, we adopted a dual approach combining molecular modeling and biological studies, in order to assess the interaction between four selected natural antioxidants (NAs; berberine, curcumin, astaxanthin, indicaxanthin) and tissue transglutaminase (TG2) levels both in the absence and in the presence of full native peptide of amyloid\u2010\u03b2 (A\u03b2). Docking studies were performed to ascertain the binding affinity of NAs against the TG2 closed, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010bound closed, and open forms. In the biological investigation, the effect of berberine and curcumin treatment on TG2 in Olfactory Ensheathing Cells (OECs) exposed to A\u03b2(1\u201342) or to A\u03b2(25\u201335), a A\u03b2 toxic fragment, or to reverse\u2010sequence fragment A\u03b2(35\u201325), an A\u03b2 not toxic fragment, was tested. In addition, their effect on the percentage of cell viability and cytoskeleton marker (GFAP, vimentin and nestin) levels were evaluated. The role of berberine and curcumin on both endocellular levels of reactive oxygen species (ROS) and apoptotic pathway activation were also assessed. Our findings demonstrate that pretreatment of OECs with these NAs counteracted the A\u03b2\u2010induced upregulation of TG2, restoring its expression to control levels and preserving its predominant cytosolic localization. Furthermore, antioxidant pretreatment reinstated cell viability, normalized the expression of GFAP, vimentin, and nestin, reduced intracellular ROS accumulation, and prevented activation of the apoptotic cascade. Our findings demonstrate that integrating computational and biological approaches, enhances the identification of potent therapeutic agents and also highlights berberine and curcumin as promising candidates for the development of novel neuroprotective drugs against neurodegenerative disorders, including Alzheimer's disease.\n                  <\/jats:p>","DOI":"10.1002\/biof.70088","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:02:28Z","timestamp":1772989348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulatory Effect of Natural Antioxidants on Tissue Transglutaminase Levels in Olfactory Ensheathing Cells Exposed to Amyloid\u2010\u03b2: Integrated Biochemical and Computational Analysis"],"prefix":"10.1002","volume":"52","author":[{"given":"Rosalia","family":"Pellitteri","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tomasella","sequence":"additional","affiliation":[{"name":"Polo Universitario Dell'annunziata, Dottorato in Scienze Veterinarie, University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Assunta","family":"Chiacchio","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, Section of Biochemistry University of Catania  Catania Italy"},{"name":"CERNUT, Research Centre for Nutraceuticals and Health Products, University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pappalardo","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, Section of Biochemistry University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Legnani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences University of Milano Bicocca  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Spatuzza","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6182-8608","authenticated-orcid":false,"given":"Alessandro","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Guccione","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, Section of Biochemistry University of Catania  Catania Italy"},{"name":"CERNUT, Research Centre for Nutraceuticals and Health Products, University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9808-4681","authenticated-orcid":false,"given":"Agatina","family":"Campisi","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, Section of Biochemistry University of Catania  Catania Italy"},{"name":"CERNUT, Research Centre for Nutraceuticals and Health Products, University of Catania  Catania 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