{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:12:06Z","timestamp":1791241926908,"version":"4.1.0"},"reference-count":98,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Parkinson's disease (PD) is the fastest growing neurodegenerative disorder worldwide. Available treatments are only symptomatic, urging the demand for new therapies. Ferroptosis is increasingly reported as a critical player in neurodegeneration. Meanwhile, ferroptosis is activated by impaired mitophagy under rigorous milieu of oxidative stress that disrupts mitochondrial homeostasis. However, the interplay between ferroptosis and mitophagy is not fully elucidated in PD. Carvedilol is a cardiovascular antioxidant, antiferroptotic drug with lipophilic nature that allows its passage via blood brain barrier. Moreover, its effect on modulating mitochondrial balance is emerging in multiple disorders. Therefore, This study aimed to explore the possible neuroprotective mechanistic effects of carvedilol on rotenone\u2010induced PD rat model in context of ferroptosis\u2010mitophagy interaction. Rotenone\u2010induced toxicities were detected by Immunohistochemistry, ELISA, qPCR and western blot analysis techniques. Rotenone disrupted key players of ferroptosis\u2010mitophagy axes. Nrf2, Glutathione peroxidase (GPX4), Catalase, PINK 1\/PARKIN levels were drastically decreased. Acyl coA synthetase long chain (ACSL4), MDA and NF\u2010\u03baB levels were significantly increased. Contrarily, carvedilol preserved adequate Nrf2, GPX4, PINK1 and PARKIN levels and increased catalase. Furthermore, it downregulated ACSL4, reduced NF\u2010\u03baB and MDA levels to maintain normal mitophagy and inhibit ferroptosis. Carvedilol's protective effects extended to alleviate \u03b1\u2010synuclein and upregulate tyrosine hydroxylase in the striata and substantia nigra leading to distinguished improvements of motor functions. To the best of our knowledge, this is the first study to highlight carvedilol's neuroprotective capacity against PD pathologies in terms of ferroptosis \u2010 mitophagy interaction as a novel therapeutic approach to tackle PD at earlier stages.<\/jats:p>","DOI":"10.1002\/jbt.70607","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T09:22:32Z","timestamp":1763371352000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Carvedilol Confers Neuroprotective Activity Through Modulating Ferroptosis Key Players and PINK1\/PARKIN Mediated Mitophagy in an Experimental Parkinson's Rat Model"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7775-2281","authenticated-orcid":false,"given":"Nermeen Z.","family":"Abuelezz","sequence":"first","affiliation":[{"name":"Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing Misr 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