{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:33Z","timestamp":1792789413187,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UAE University (UAEU), United Arab Emirates, Al Ain, UAE","award":["#12R210"],"award-info":[{"award-number":["#12R210"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease is a neurodegenerative disorder that affects the elderly population worldwide. Rotenone (ROT) is an environmental toxin that impairs mitochondrial dynamics by inhibiting respiratory chain complex I and thus inducing oxidative stress. Farnesol (FSL) is a dietary sesquiterpene with antioxidant and anti-inflammatory properties reported in various in vivo models. To evaluate the efficacy of FSL in the management of PD, Wistar rats were injected with ROT (2.5 mg\/kg, i.p) and pretreated with FSL. Immunohistochemical staining measured tyrosine hydroxylase-positive cells in the substantia nigra and striatum. Western blotting was employed to determine protein expression of inflammatory, apoptotic, and autophagic markers. Our results indicate that FSL significantly protected against ROT-induced inflammation by suppressing microglial and astrocytic activation through the downregulation of Toll-Like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB), inhibitor of kappa B (IkB), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), matrix metalloproteinase-9 (MMP-9) expression. FSL has also demonstrated an antioxidant effect by enhancing the activity of superoxide dismutase and catalase while reducing the level of Malondialdehyde and nitric oxide. Moreover, it restored homeostasis in ROT-induced imbalance between pro- and anti-apoptotic proteins. Impaired autophagy observed in ROT-injected rats was corrected by FSL treatment, which upregulated phosphorylated mammalian target of rapamycin (p-mTOR) expression and downregulated P62, an autophagosome marker. The protective effect of FSL was further supported by preserving the brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase in the brain. These findings demonstrate the neuroprotective ability of FSL and its potential to be developed as a pharmaceutical or nutraceutical agent for the prevention and treatment of PD by mitigating neuropathological changes observed in dopaminergic neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms27020811","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:03:10Z","timestamp":1768381390000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Farnesol, a Dietary Sesquiterpene, Attenuates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Oxidative Stress, Inflammation, and Apoptosis via Mediation of Cell Signaling Pathways in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-8756","authenticated-orcid":false,"given":"Lujain","family":"Bader Eddin","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seenipandi","family":"Arunachalam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-7164","authenticated-orcid":false,"given":"Sheikh","family":"Azimullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Department of Pharmaceutical Biosciences, Drug Safety and Toxicology, Uppsala Biomedicines Centrum BMC, Husarg, 75124 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-7372","authenticated-orcid":false,"given":"Mohamed Fizur","family":"Nagoor Meeran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-3637","authenticated-orcid":false,"given":"Mouza Ali Hasan AlQaishi","family":"Alshehhi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Mahgoub","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Beiram","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-2966","authenticated-orcid":false,"given":"Shreesh","family":"Ojha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Zayed Bin Sultan Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","first-page":"461","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Park. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.expneurol.2005.01.013","article-title":"Oxidative stress and inflammation in Parkinson\u2019s disease: Is there a causal link?","volume":"193","author":"Hald","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lecours, C., Bordeleau, M., Cantin, L., Parent, M., Paolo, T.D., and Tremblay, M. (2018). 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