{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:09:45Z","timestamp":1778303385733,"version":"3.51.4"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aggregation and seeded propagation of \u03b1-synuclein (\u03b1-syn) are central to the pathogenesis of Parkinson\u2019s disease and related synucleionopathies. Modulation of seeded aggregation and amplification of pathological \u03b1-syn species represents a promising strategy for limiting disease progression. Here, we investigated the effects of naturally derived polyphenolic compounds on \u03b1-syn fibrillation, seeded aggregation, and associated cytotoxicity. Among the compounds examined, salvianolic acid B and dihydromyricetin exhibited significant inhibitory effects on \u03b1-syn aggregation. Biochemical and biophysical analyses using Thioflavin-T fluorescence, Congo Red binding, and transmission electron microscopy demonstrated that both compounds inhibited fibril formation and altered fibril morphology. Notably, dihydromyricetin efficiently disaggregated preformed fibrils and suppressed seeded fibril elongation, whereas salvianolic acid B primarily delayed aggregation kinetics. Both compounds significantly reduced \u03b1-syn-induced cytotoxicity in BE(2)-M17 cells. These findings demonstrate that salvianolic acid B and dihydromyricetin differentially modulate key steps in the \u03b1-syn aggregation pathway and reduce associated cellular toxicity. Collectively, these results provide mechanistic insight into the modulation of seeded \u03b1-syn aggregation and identify salvianolic acid B and dihydromyricetin as effective modulators of pathological \u03b1-syn assembly.<\/jats:p>","DOI":"10.3390\/ijms27093843","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Molecular Mechanisms Underlie Modulation of Seeded \u03b1-Synuclein Aggregation and Toxicity by Salvianolic Acid B and Dihydromyricetin"],"prefix":"10.3390","volume":"27","author":[{"given":"Nishant N.","family":"Vaikath","sequence":"first","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-7108","authenticated-orcid":false,"given":"Iman W.","family":"Achkar","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indulekha P.","family":"Sudhakaran","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilham Y.","family":"Abdi","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janarthanan","family":"Ponraj","sequence":"additional","affiliation":[{"name":"Materials Core Laboratoires (MCL), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8084","authenticated-orcid":false,"given":"Omar M. A.","family":"El-Agnaf","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrn.2016.178","article-title":"Selective Neuronal Vulnerability in Parkinson Disease","volume":"18","author":"Surmeier","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson Disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-Synuclein in Lewy Bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pitton Rissardo, J., McGarry, A., Shi, Y., Fornari Caprara, A.L., and Kannarkat, G.T. (2025). Alpha-Synuclein Neurobiology in Parkinson\u2019s Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives. Brain Sci., 15.","DOI":"10.3390\/brainsci15121260"},{"key":"ref_5","first-page":"S51","article-title":"The Synucleinopathies: Twenty Years On","volume":"7","author":"Goedert","year":"2017","journal-title":"J. Park. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-023-05672-9","article-title":"Alpha-Synuclein in Parkinson\u2019s Disease and Other Synucleinopathies: From Overt Neurodegeneration Back to Early Synaptic Dysfunction","volume":"14","author":"Calabresi","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41582-024-01043-w","article-title":"\u03b1-Synuclein Pathology as a Target in Neurodegenerative Diseases","volume":"21","author":"Park","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a041644","DOI":"10.1101\/cshperspect.a041644","article-title":"Animal Models of Parkinson\u2019s Disease","volume":"15","author":"Dawson","year":"2025","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41531-025-00887-3","article-title":"A Personalised and Comprehensive Approach Is Required to Suppress or Replenish SNCA for Parkinson\u2019s Disease","volume":"11","author":"Li","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/s41580-018-0060-8","article-title":"A New Era for Understanding Amyloid Structures and Disease","volume":"19","author":"Iadanza","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1017\/S0033583516000172","article-title":"Secondary Nucleation of Monomers on Fibril Surface Dominates \u03b1-Synuclein Aggregation and Provides Autocatalytic Amyloid Amplification","volume":"50","author":"Gaspar","year":"2017","journal-title":"Q. Rev. Biophys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2313465121","DOI":"10.1073\/pnas.2313465121","article-title":"Modulation of \u03b1-Synuclein in Vitro Aggregation Kinetics by Its Alternative Splice Isoforms","volume":"121","author":"Toprakcioglu","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/B978-0-444-63945-5.00017-9","article-title":"Prion-like Propagation of Pathology in Parkinson Disease","volume":"153","author":"Brundin","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.molmed.2020.03.012","article-title":"Cell-to-Cell Transmission of Tau and \u03b1-Synuclein","volume":"26","author":"Uemura","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41531-023-00618-6","article-title":"Cell-to-Cell Transmitted Alpha-Synuclein Recapitulates Experimental Parkinson\u2019s Disease","volume":"10","author":"Prymaczok","year":"2024","journal-title":"npj Park. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41531-025-01080-2","article-title":"Impact of \u03b1-Synuclein Fibril Structure on Seeding Activity in Experimental Models of Parkinson\u2019s Disease","volume":"11","author":"Ohira","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11266","DOI":"10.1038\/s41467-025-66146-4","article-title":"Seed Amplification of MSA Alpha-Synuclein Aggregates Preserves the Biological and Structural Properties of Brain-Derived Aggregates","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s10571-025-01544-2","article-title":"Alpha-Synuclein Pathophysiology in Neurodegenerative Disorders: A Review Focusing on Molecular Mechanisms and Treatment Advances in Parkinson\u2019s Disease","volume":"45","author":"Yaribash","year":"2025","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100179","DOI":"10.1016\/j.bbadva.2025.100179","article-title":"Hidden Faces of Alpha-Synuclein: Cryo-EM Revelation of Fibril Polymorphs Driven by Disease, Mutations, and PTMs","volume":"9","author":"Pirhaghi","year":"2026","journal-title":"BBA Adv."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, T., Zhao, M., Li, P., Liu, T., and Xie, J. (2025). Pharmacological Mechanisms and Potential Clinical Applications of Dihydromyricetin in Neurological Disorders. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1618623"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/cbic.201000604","article-title":"Baicalein Inhibits Formation of \u03b1-Synuclein Oligomers within Living Cells and Prevents A\u03b2 Peptide Fibrillation and Oligomerisation","volume":"12","author":"Lu","year":"2011","journal-title":"Chembiochem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.ijbiomac.2022.08.088","article-title":"Baicalein Exhibits Differential Effects and Mechanisms towards Disruption of \u03b1-Synuclein Fibrils with Different Polymorphs","volume":"220","author":"Yao","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Stylianopoulou, E., Daviti, A., Giourou, V., Gerasimidi, E., Nikolaou, A., Kourkoutas, Y., Grigoriou, M.E., Paleologou, K.E., and Skavdis, G. (2023). Assessment of the Anti-Amyloidogenic Properties of Essential Oils and Their Constituents in Cells Using a Whole-Cell Recombinant Biosensor. Brain Sci., 14.","DOI":"10.3390\/brainsci14010035"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111556","DOI":"10.1016\/j.biopha.2021.111556","article-title":"Baicalein Alleviates Depression-like Behavior in Rotenone- Induced Parkinson\u2019s Disease Model in Mice through Activating the BDNF\/TrkB\/CREB Pathway","volume":"140","author":"Zhao","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/j.bbadis.2016.07.008","article-title":"Baicalein Inhibits \u03b1-Synuclein Oligomer Formation and Prevents Progression of \u03b1-Synuclein Accumulation in a Rotenone Mouse Model of Parkinson\u2019s Disease","volume":"1862","author":"Hu","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.33549\/physiolres.934929","article-title":"6-Hydroxydopamine-Induced Neurotoxicity in Rat Model of Parkinson\u2019s Disease: Is Reversed via Anti-Oxidative Activities of Curcumin and Aerobic Exercise Therapy","volume":"71","author":"Sokouti","year":"2022","journal-title":"Physiol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117529","DOI":"10.1016\/j.bmc.2023.117529","article-title":"4-Arylidene Curcumin Derivatives in Vitro Inhibit \u03b1-Synuclein Aggregation and Disaggregate the Preformed Fibril","volume":"96","author":"Liu","year":"2023","journal-title":"Bioorg. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, J.-F., Jiang, Z.-Q., Cao, S., Zhang, M.-X., Wang, L.-H., Liu, J., Lu, Y.-H., Wang, H.-Y., Hong, X.-J., and Wang, Z.-G. (2024). Curcumin Inhibits \u03b1-Synuclein Aggregation by Acting on Liquid-Liquid Phase Transition. Foods, 13.","DOI":"10.3390\/foods13091287"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhytniakivska, O., Chaturvedi, T., and Thomsen, M.H. (2025). Plant-Based Inhibitors of Protein Aggregation. Biomolecules, 15.","DOI":"10.3390\/biom15040481"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3946","DOI":"10.1021\/acs.jafc.9b00922","article-title":"Dihydromyricetin Inhibits \u03b1-Synuclein Aggregation, Disrupts Preformed Fibrils, and Protects Neuronal Cells in Culture against Amyloid-Induced Cytotoxicity","volume":"67","author":"Jia","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107379","DOI":"10.1016\/j.bpc.2024.107379","article-title":"Salvianolic Acid B Prevents the Amyloid Transformation of A53T Mutant of \u03b1-Synuclein","volume":"318","author":"Akhtar","year":"2025","journal-title":"Biophys. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1142\/S0192415X2450054X","article-title":"Chinese Medicine-Derived Salvianolic Acid B for Disease Therapy: A Scientometric Study","volume":"52","author":"Zhao","year":"2024","journal-title":"Am. J. Chin. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bi, S., Liu, S., Zhu, K., Gao, D., Chen, L., Yu, C., and Liang, G. (2025). Preclinical and Experimental Evidence of Salvianolic Acid B in the Treatment of Neurological Diseases. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1606146"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s12032-025-02892-1","article-title":"Salvianolic Acid B in Cancer Therapy: Pharmacokinetic Profile, Anticancer Mechanisms and Translational Potential","volume":"42","author":"Chanda","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Shao, Y., Zhai, L., Jiang, S., Sun, F., and Liu, X. (2025). Salvianolic Acid B: A Promising Cardioprotective Agent. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1681358"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"172888","DOI":"10.1016\/j.ejphar.2019.172888","article-title":"Multitarget and Promising Role of Dihydromyricetin in the Treatment of Metabolic Diseases","volume":"870","author":"Tong","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e15977","DOI":"10.7717\/peerj.15977","article-title":"Progress in the Mechanism of Autophagy and Traditional Chinese Medicine Herb Involved in Alcohol-Related Liver Disease","volume":"11","author":"Han","year":"2023","journal-title":"PeerJ"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, Z., Cao, Z., Yue, Z., and Yang, Z. (2023). Research Progress of Dihydromyricetin in the Treatment of Diabetes Mellitus. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1216907"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"He, C., Chen, Y., Xie, J., Luo, M., Fisher, D., Hien, N.T.T., Musabaev, E., Dang, Y., Zhao, L., and Xia, Y. (2024). Dihydromyricetin: An Emerging Compound with Comprehensive Effects on Multiple Systems. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1488003"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12345","DOI":"10.1021\/bi00164a008","article-title":"Amyloid Fibril Formation Requires a Chemically Discriminating Nucleation Event: Studies of an Amyloidogenic Sequence from the Bacterial Protein OsmB","volume":"31","author":"Jarrett","year":"1992","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8972","DOI":"10.1021\/bi9904149","article-title":"Assembly of A Beta Amyloid Protofibrils: An in Vitro Model for a Possible Early Event in Alzheimer\u2019s Disease","volume":"38","author":"Harper","year":"1999","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0092-8674(93)90635-4","article-title":"Seeding \u201cOne-Dimensional Crystallization\u201d of Amyloid: A Pathogenic Mechanism in Alzheimer\u2019s Disease and Scrapie?","volume":"73","author":"Jarrett","year":"1993","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev.biochem.66.1.385","article-title":"Models of Amyloid Seeding in Alzheimer\u2019s Disease and Scrapie: Mechanistic Truths and Physiological Consequences of the Time-Dependent Solubility of Amyloid Proteins","volume":"66","author":"Harper","year":"1997","journal-title":"Annu. Rev. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuron.2011.08.033","article-title":"Exogenous \u03b1-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death","volume":"72","author":"Luk","year":"2011","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0140-6736(23)01419-8","article-title":"The Epidemiology of Parkinson\u2019s Disease","volume":"403","author":"Darweesh","year":"2024","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"Alpha-Synuclein in Filamentous Inclusions of Lewy Bodies from Parkinson\u2019s Disease and Dementia with Lewy Bodies","volume":"95","author":"Spillantini","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrneurol.2012.242","article-title":"100 Years of Lewy Pathology","volume":"9","author":"Goedert","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.bbapap.2019.03.001","article-title":"\u03b1-Synuclein Misfolding and Aggregation: Implications in Parkinson\u2019s Disease Pathogenesis","volume":"1867","author":"Mehra","year":"2019","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19509","DOI":"10.1074\/jbc.274.28.19509","article-title":"Alpha-Synuclein Fibrillogenesis Is Nucleation-Dependent. Implications for the Pathogenesis of Parkinson\u2019s Disease","volume":"274","author":"Wood","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s00018-022-04166-9","article-title":"Effects of Oligomer Toxicity, Fibril Toxicity and Fibril Spreading in Synucleinopathies","volume":"79","author":"Cascella","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s40478-018-0587-0","article-title":"Rapid Dissemination of Alpha-Synuclein Seeds through Neural Circuits in an in-Vivo Prion-like Seeding Experiment","volume":"6","author":"Okuzumi","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104623","DOI":"10.1016\/j.nbd.2019.104623","article-title":"Neural Connectivity Predicts Spreading of Alpha-Synuclein Pathology in Fibril-Injected Mouse Models: Involvement of Retrograde and Anterograde Axonal Propagation","volume":"134","author":"Mezias","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0925-4439(00)00034-X","article-title":"Approaches to Discovery and Characterization of Inhibitors of Amyloid Beta-Peptide Polymerization","volume":"1502","author":"Findeis","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1042\/BST0331106","article-title":"Alpha-Synuclein Aggregation in Neurodegenerative Diseases and Its Inhibition as a Potential Therapeutic Strategy","volume":"33","author":"Paleologou","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.expneurol.2017.10.003","article-title":"Therapeutic Approaches to Target Alpha-Synuclein Pathology","volume":"298","author":"Brundin","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-025-00797-1","article-title":"Emerging Targets of \u03b1-Synuclein Spreading in \u03b1-Synucleinopathies: A Review of Mechanistic Pathways and Interventions","volume":"20","author":"Kuo","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1046\/j.1471-4159.2003.01976.x","article-title":"Potent Anti-Amyloidogenic and Fibril-Destabilizing Effects of Polyphenols in Vitro: Implications for the Prevention and Therapeutics of Alzheimer\u2019s Disease","volume":"87","author":"Ono","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1747-0285.2005.00318.x","article-title":"Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism","volume":"67","author":"Porat","year":"2006","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1471-4159.2006.03707.x","article-title":"Antioxidant Compounds Have Potent Anti-Fibrillogenic and Fibril-Destabilizing Effects for Alpha-Synuclein Fibrils in Vitro","volume":"97","author":"Ono","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.febslet.2011.03.046","article-title":"Inhibition and Disaggregation of \u03b1-Synuclein Oligomers by Natural Polyphenolic Compounds","volume":"585","author":"Caruana","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Phan, H.T.T., Samarat, K., Takamura, Y., Azo-Oussou, A.F., Nakazono, Y., and Vestergaard, M.C. (2019). Polyphenols Modulate Alzheimer\u2019s Amyloid Beta Aggregation in a Structure-Dependent Manner. Nutrients, 11.","DOI":"10.3390\/nu11040756"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Vicente-Zurdo, D., G\u00f3mez-Mej\u00eda, E., Rosales-Conrado, N., and Le\u00f3n-Gonz\u00e1lez, M.E. (2024). A Comprehensive Analytical Review of Polyphenols: Evaluating Neuroprotection in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115906"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.nbd.2014.11.007","article-title":"Ginsenoside Rb1 Inhibits Fibrillation and Toxicity of Alpha-Synuclein and Disaggregates Preformed Fibrils","volume":"74","author":"Ardah","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15741","DOI":"10.1007\/s12035-025-05208-6","article-title":"Oleuropein Aglycone, an Olive Polyphenol, Influences Alpha-Synuclein Aggregation and Exerts Neuroprotective Effects in Different Parkinson\u2019s Disease Models","volume":"62","author":"Basellini","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12154-009-0027-5","article-title":"Binding Mode of Thioflavin T and Other Molecular Probes in the Context of Amyloid Fibrils-Current Status","volume":"3","author":"Groenning","year":"2010","journal-title":"J. Chem. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1126\/science.1079469","article-title":"Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis","volume":"300","author":"Kayed","year":"2003","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1038\/s41467-022-33252-6","article-title":"Small Soluble \u03b1-Synuclein Aggregates Are the Toxic Species in Parkinson\u2019s Disease","volume":"13","author":"Emin","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40035-024-00401-4","article-title":"\u03b1-Synuclein Oligomers Potentiate Neuroinflammatory NF-\u03baB Activity and Induce Cav3.2 Calcium Signaling in Astrocytes","volume":"13","author":"Leandrou","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nsmb.1437","article-title":"EGCG Redirects Amyloidogenic Polypeptides into Unstructured, off-Pathway Oligomers","volume":"15","author":"Ehrnhoefer","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7710","DOI":"10.1073\/pnas.0910723107","article-title":"EGCG Remodels Mature Alpha-Synuclein and Amyloid-Beta Fibrils and Reduces Cellular Toxicity","volume":"107","author":"Bieschke","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3843\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:13:40Z","timestamp":1778300020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,26]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27093843"],"URL":"https:\/\/doi.org\/10.3390\/ijms27093843","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,26]]}}}