{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:54:49Z","timestamp":1775710489263,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["22401192"],"award-info":[{"award-number":["22401192"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["U25A20597"],"award-info":[{"award-number":["U25A20597"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular antioxidant response and a promising therapeutic target for Parkinson\u2019s disease (PD). Resibufogenin (RBG), a bioactive bufadienolide from toad venom, has been identified as a potential Nrf2 agonist; however, its application is limited by cytotoxicity and poor drug-like properties. Herein, we report the rational design, synthesis, and biological evaluation of a series of RBG derivatives modified at the C3, C14\u2013C15, and C17 positions. Systematic structure\u2013activity relationship (SAR) studies identified 2-5c, featuring a C3 2-chloroacryloyl group and a C17 pyrimidine substitution, as a potential Nrf2 activator (EC50 = 4.18 \u03bcM), exhibiting approximately 7-fold greater activity than RBG. Importantly, 2-5c demonstrated neuroprotective effects in MPP+-induced BV2 microglial cells and effectively ameliorated motor deficits in an MPTP-induced PD mouse model. These findings suggest that 2-5c represents a promising candidate for further investigation in the development of novel Nrf2-based therapies for PD.<\/jats:p>","DOI":"10.3390\/ijms27073326","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:40:31Z","timestamp":1775554831000},"page":"3326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Biological Evaluation of RBG Derivatives as Nrf2 Activators for the Treatment of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Wen-Qing","family":"Shi","sequence":"first","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Hua","family":"Zhuang","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-Heng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo-Qiang","family":"Lin","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"The Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaopeng","family":"Yu","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Huan","family":"Fu","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiange","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3086-8372","authenticated-orcid":false,"given":"Shoujiao","family":"Peng","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gu-Zhou","family":"Chen","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5982-2349","authenticated-orcid":false,"given":"Wenbo","family":"Ye","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9926","DOI":"10.1073\/pnas.91.21.9926","article-title":"Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2\/AP1 repeat of the beta-globin locus control region","volume":"91","author":"Moi","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1128\/MCB.15.8.4184","article-title":"Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins","volume":"15","author":"Itoh","year":"1995","journal-title":"Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1101\/gad.13.1.76","article-title":"Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain","volume":"13","author":"Itoh","year":"1999","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00099-20","DOI":"10.1128\/MCB.00099-20","article-title":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tips.2022.12.003","article-title":"Advances and challenges in therapeutic targeting of NRF2","volume":"44","author":"Copple","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41573-025-01145-0","article-title":"Thirty years of NRF2: Advances and therapeutic challenges","volume":"24","author":"Zhang","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Amoroso, R., Maccallini, C., and Bellezza, I. (2023). Activators of Nrf2 to counteract neurodegenerative diseases. Antioxidants, 12.","DOI":"10.3390\/antiox12030778"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119048","DOI":"10.1016\/j.biopha.2026.119048","article-title":"Involvement of Keap1\/Nrf2 and the antioxidant defence in cytoprotective effects induced by cannabis polyphenols in SH-SY5Y neuronal cells","volume":"196","author":"Ventura","year":"2026","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4103\/JAPTR.JAPTR_313_24","article-title":"Potential of rutin from Rhizophora mucronata leaves as an inhibitor of Kelch-like ECH-associated protein 1\/Nuclear factor erythroid 2 related factor 2 (Keap1\/Nrf2): An in silico study for Alzheimer\u2019s therapy","volume":"16","author":"Saputri","year":"2025","journal-title":"Adv. Pharm. Technol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1021\/acschemneuro.5c00540","article-title":"Neuroprotective effects of a 3-Amino quinazoline derivative via Keap1\u2013Nrf2 Pathway activation in an ICV-STZ-induced rat model of sporadic Alzheimer\u2019s Disease","volume":"16","author":"Maheta","year":"2025","journal-title":"ACS Chem. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105325","DOI":"10.1016\/j.neuint.2022.105325","article-title":"The principal molecular mechanisms behind the activation of Keap1\/Nrf2\/ARE pathway leading to neuroprotective action in Parkinson\u2019s disease","volume":"156","author":"Chakkittukandiyil","year":"2022","journal-title":"Neurochem. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117172","DOI":"10.1016\/j.taap.2024.117172","article-title":"Synthesis and evaluation of novel ethyl ferulate derivatives as potent Keap1 inhibitors to activate the Nrf2\/ARE pathway in Parkinson\u2019s disease","volume":"494","author":"Chakkittukandiyil","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15539","DOI":"10.1038\/s41598-023-42813-8","article-title":"Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson\u2019s disease","volume":"13","author":"Xia","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106654","DOI":"10.1016\/j.bioorg.2023.106654","article-title":"Novel flavonoid 1,3,4-oxadiazole derivatives ameliorate MPTP-induced Parkinson\u2019s disease via Nrf2\/NF-\u03baB signaling pathway","volume":"138","author":"Meng","year":"2023","journal-title":"Bioorg. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102103","DOI":"10.1016\/j.jchemneu.2022.102103","article-title":"The neuroprotective effects of paeoniflorin against MPP+-induced damage to dopaminergic neurons via the Akt\/Nrf2\/GPX4 pathway","volume":"122","author":"Wang","year":"2022","journal-title":"J. Chem. Neuroanat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s12640-022-00521-7","article-title":"Apigenin Attenuates Functional and Structural Alterations via Targeting NF-kB\/Nrf2 Signaling Pathway in LPS-Induced Parkinsonism in Experimental Rats","volume":"40","author":"Patel","year":"2022","journal-title":"Neurotox. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, Q.X., Zhou, L., Long, T., Qin, D.L., Wang, Y.L., Ye, Y., Zhou, X.G., Wu, J.M., and Wu, A.G. (2022). Galangin Exhibits Neuroprotective Effects in 6-OHDA-Induced Models of Parkinson\u2019s Disease via the Nrf2\/Keap1 Pathway. Pharmaceuticals, 15.","DOI":"10.3390\/ph15081014"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5455","DOI":"10.1007\/s11033-023-08409-1","article-title":"Targeting Nrf2 signaling pathway and oxidative stress by resveratrol for Parkinson\u2019s disease: An overview and update on new developments","volume":"50","author":"Zamanian","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11011-024-01452-2","article-title":"Emerging role of Nrf2 in Parkinson\u2019s disease therapy: A critical reassessment","volume":"40","author":"Sharma","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1007\/s10787-025-01917-5","article-title":"A systematic review of natural products targeting Nrf2-Keap1-ARE pathway and their influence on neurodegenerative disorders","volume":"33","author":"Gote","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1007\/s11064-024-04116-w","article-title":"Salidroside Mediated the Nrf2\/GPX4 Pathway to Attenuates Ferroptosis in Parkinson\u2019s Disease","volume":"49","author":"Shen","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5398542","DOI":"10.1155\/2017\/5398542","article-title":"Salidroside Protects against MPP+-Induced Neuronal Injury through DJ-1-Nrf2 Antioxidant Pathway","volume":"2017","author":"Wu","year":"2017","journal-title":"Evid. Based Complement. Alternat Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chiang, M.C., Yang, Y.P., Nicol, C.J.B., Chiang, T., and Yen, C. (2025). Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells. Life, 15.","DOI":"10.3390\/life15020294"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9603271231220610","DOI":"10.1177\/09603271231220610","article-title":"Ginsenoside Rk1 prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson\u2019s disease via activating silence information regulator 3-mediated Nrf2\/HO-1 signaling pathway","volume":"42","author":"Ren","year":"2023","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s11064-015-1751-6","article-title":"Neuroprotective Effects of Tanshinone I Against 6-OHDA-Induced Oxidative Stress in Cellular and Mouse Model of Parkinson\u2019s Disease Through Upregulating Nrf2","volume":"41","author":"Jing","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.neuroscience.2015.06.030","article-title":"Tanshinone IIA protects dopaminergic neurons against 6-hydroxydopamine-induced neurotoxicity through miR-153\/NF-E2-related factor 2\/antioxidant response element signaling pathway","volume":"303","author":"Zhang","year":"2015","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1021\/acs.jafc.7b04641","article-title":"Comparison of Adaptive Neuroprotective Mechanisms of Sulforaphane and its Interconversion Product Erucin in in Vitro and in Vivo Models of Parkinson\u2019s Disease","volume":"66","author":"Morroni","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","first-page":"847","article-title":"Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K\/Akt-dependent manner","volume":"5","author":"Deng","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_31","first-page":"1412","article-title":"Curcumin Modulates p62-Keap1-Nrf2-Mediated Autophagy in Rotenone-Induced Parkinson\u2019s Disease Mouse Models","volume":"14","author":"Rathore","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhong, L., Cai, B., Wang, Q., Li, X., Xu, W., and Chen, T. (2022). Exploring the Neuroprotective Mechanism of Curcumin Inhibition of Intestinal Inflammation against Parkinson\u2019s Disease Based on the Gut-Brain Axis. Pharmaceuticals, 16.","DOI":"10.3390\/ph16010039"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1021\/acschemneuro.0c00363","article-title":"Novel Curcumin-Diethyl Fumarate Hybrid as a Dualistic GSK-3\u03b2 Inhibitor\/Nrf2 Inducer for the Treatment of Parkinson\u2019s Disease","volume":"11","author":"Pruccoli","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.3892\/ijo.2011.1310","article-title":"Apoptotic and anti-metastatic effects of the whole skin of Venenum bufonis in A549 human lung cancer cells","volume":"40","author":"Park","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Z.J., Sun, L., and Heinbockel, T. (2014). Resibufogenin and cinobufagin activate central neurons through an ouabain-like action. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113272"},{"key":"ref_36","unstructured":"Chinese Pharmacopoeia Commission (2020). Pharmacopoeia of the People\u2019s Republic of China, China Medical Science Press. [9th ed.]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.apsb.2018.07.007","article-title":"Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1","volume":"8","author":"Tian","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zou, D., Wang, Q., Chen, T., Sang, D., Yang, T., Wang, Y., Gao, M., He, F., Li, Y., and He, L. (2022). Bufadienolides originated from toad source and their anti-inflammatory activity. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1044027"},{"key":"ref_39","first-page":"449","article-title":"Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-D-\u03b1-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy","volume":"11","author":"Chu","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_40","first-page":"e942783","article-title":"Resibufogenin: An Emerging Therapeutic Compound with Multifaceted Pharmacological Effects\u2014A Comprehensive Review","volume":"30","author":"Zhang","year":"2024","journal-title":"Med. Sci. Monit."},{"key":"ref_41","first-page":"289","article-title":"Cardiac toxicity of resibufogenin: Electrophysiological evidence","volume":"22","author":"Xie","year":"2001","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_42","first-page":"557","article-title":"The monophasic action potential technique and its application in cardiac electropharmacology","volume":"15","author":"Xie","year":"1993","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_43","first-page":"97","article-title":"Induction of delayed afterdepolarizations and triggered arrhythmias in isolated Purkinje fibers: Comparison of resibufogenin and acetylstrophanthidin","volume":"15","author":"Xie","year":"1994","journal-title":"Acta Pharm. Sin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"399","DOI":"10.15171\/apb.2016.052","article-title":"Improvement of Meloxicam Solubility Using a \u03b2-Cyclodextrin Complex Prepared via the Kneading Method and Incorporated into an Orally Disintegrating Tablet","volume":"6","author":"Ainurofiq","year":"2016","journal-title":"Adv. Pharm. Bull."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dadej, A., Wo\u017aniak-Braszak, A., Bilski, P., Piotrowska-Kempisty, H., J\u00f3zkowiak, M., Geszke-Moritz, M., Moritz, M., Dadej, D., and Jeli\u0144ska, A. (2021). Modification of the Release of Poorly Soluble Sulindac with the APTES-Modified SBA-15 Mesoporous Silica. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101693"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1080\/10286020.2011.597385","article-title":"Novel microbial transformation of resibufogenin by Fusarium solani","volume":"13","author":"Xin","year":"2011","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9704","DOI":"10.1021\/acs.orglett.4c03433","article-title":"Scalable Protecting-Group-Free Total Synthesis of Resibufogenin and Bufalin","volume":"26","author":"Yu","year":"2024","journal-title":"Org. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41401-025-01689-2","article-title":"Resibufogenin ameliorates cerebral ischemia-reperfusion injury by modulating microglial redox homeostasis via Keap1-Nrf2-TFR1\/ARE axis","volume":"47","author":"Chen","year":"2026","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103324","DOI":"10.1016\/j.redox.2024.103324","article-title":"Z-ligustilide provides a neuroprotective effect by regulating the phenotypic polarization of microglia via activating Nrf2-TrxR axis in the Parkinson\u2019s disease mouse model","volume":"76","author":"Peng","year":"2024","journal-title":"Redox Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"177972","DOI":"10.1016\/j.ejphar.2025.177972","article-title":"The novel GLP-1\/GIP dual agonist DA3-CH is more effective than liraglutide in the MPTP mouse model of Parkinson\u2019s disease","volume":"1003","author":"Feng","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jneumeth.2010.03.026","article-title":"A rotarod test for evaluation of motor skill learning","volume":"189","author":"Shiotsuki","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eadn4845","DOI":"10.1126\/sciadv.adn4845","article-title":"Antagonism of \u03b2-arrestins in IL-4-driven microglia reactivity via the Samd4\/mTOR\/OXPHOS axis in Parkinson\u2019s disease","volume":"10","author":"Liu","year":"2024","journal-title":"Sci. Adv."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:30:30Z","timestamp":1775709030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073326"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073326","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]}}}