{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:27:50Z","timestamp":1783711670301,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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                    Parkinson's disease (PD) is a progressive neurodegenerative disorder. An essential early hallmark of PD is disrupted mitochondrial dynamics driven by impaired cellular energy homeostasis. Therapeutic interventions restoring mitochondrial function and biogenesis hold promise for neuroprotection in PD. In the present study, the neuroprotective effects of formononetin (FMN) were evaluated in both MPP\n                    <jats:sup>+<\/jats:sup>\n                    \u2010induced SH\u2010SY5Y cells and the MPTP\u2010induced mouse model of Parkinson's disease, using concentrations of 5, 10, 20, and 40\u2009\u03bcM in\u00a0vitro and doses of 25 and 40\u2009mg\/kg in\u00a0vivo. To evaluate its biological activity, we employed western blotting and immunofluorescence assay to quantify the expression of disease\u2010relevant markers. Mitochondrial health was further assessed using Mitotracker, alongside reactive oxygen species (ROS) assessment. Motor behavior and molecular endpoint parameters were also measured. Our results demonstrated\u00a0that FMN significantly attenuates MPP\n                    <jats:sup>+<\/jats:sup>\n                    \/MPTP\u2010induced neurotoxicity, improves motor function, and restores the expression of PGC\u20101\u03b1, tyrosine hydroxylase, and key mitochondrial proteins involved in mitochondrial DNA replication. Enhancement of mitochondrial fusion proteins and other transcriptional regulators was also observed in the administered groups. Flow cytometry and imaging analyses confirmed that FMN\u2010mediated PGC\u20101\u03b1 activation preserves mitochondrial integrity and reduces oxidative stress. Altogether, these findings provide evidence that formononetin exerts neuroprotective effects in PD by modulating the PGC\u20101\u03b1 signaling axis.\n                  <\/jats:p>","DOI":"10.1002\/biof.70098","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:36:49Z","timestamp":1776659809000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phytoestrogenic Isoflavone Formononetin Attenuates Motor Deficits and Mitochondrial Impairment by Regulating\n                    <scp>SIRT1<\/scp>\n                    \/\n                    <scp>PGC<\/scp>\n                    \u20101\u03b1\/\n                    <scp>NRF1<\/scp>\n                    \/\n                    <scp>TFAM<\/scp>\n                    Axis in Parkinson's Disease"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9156-2189","authenticated-orcid":false,"given":"Jasleen","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and Research (NIPER\u2010R)  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6591-790X","authenticated-orcid":false,"given":"Saba","family":"Naqvi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and Research (NIPER\u2010R)  Lucknow India"},{"name":"Department of Regulatory Toxicology National Institute of Pharmaceutical Education and Research (NIPER\u2010R)  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01478-2"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2009.06.018"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03289-9"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30299-5"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.3299"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2025.101060"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S273121"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1534798"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules170910052"},{"key":"e_1_2_12_12_1","first-page":"4821","article-title":"Formononetin May Protect Aged Hearts From Ischemia\/Reperfusion Damage by Enhancing Autophagic Degradation","volume":"18","author":"Huang Z.","year":"2018","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8100430"},{"key":"e_1_2_12_14_1","article-title":"Formononetin Ameliorates Depression\u2010Like Behaviors Through Rebalancing Microglia M1\/M2 Polarization and Inhibiting NLRP3 Inflammasome: Involvement of Activating PPARalpha\u2010Mediated Autophagy","volume":"31","author":"Peng S.","year":"2025","journal-title":"Molecular Medicine (Cambridge, Mass.)"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30010196"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-025-01709-x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29225364"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1177604"},{"key":"e_1_2_12_19_1","first-page":"3615","article-title":"Decoding the Role of Nuclear Sirtuins in Parkinson's Pathogenesis","volume":"15","author":"Patel D.","year":"2024","journal-title":"ACS Chemical Neuroscience"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155285"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527318666190807160137"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2019.105414"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2021.109301"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0437-1"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109020"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00096"},{"key":"e_1_2_12_27_1","article-title":"Measuring Motor Coordination in Mice","volume":"75","author":"Deacon R. 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