{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:56:09Z","timestamp":1787313369410,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K06586"],"award-info":[{"award-number":["21K06586"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","award":["2021G021"],"award-info":[{"award-number":["2021G021"]}],"id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aggregation of \u03b1-synuclein (\u03b1-Syn) is implicated in the pathogenesis of Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Therefore, the removal of \u03b1-Syn aggregation could lead to the development of many new therapeutic agents for neurodegenerative diseases. In the present study, we succeeded in generating a new \u03b1-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on \u03b1-Syn toxicity. We found that kaempferol provided significant protection against \u03b1-Syn-related neurotoxicity. Furthermore, kaempferol induced autophagy through an increase in the biogenesis of lysosomes by inducing the expression of transcription factor EB and reducing the accumulation of \u03b1-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of \u03b1-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by \u03b1-Syn aggregates.<\/jats:p>","DOI":"10.3390\/ijms222111484","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T21:40:21Z","timestamp":1635198021000},"page":"11484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Kaempferol Has Potent Protective and Antifibrillogenic Effects for \u03b1-Synuclein Neurotoxicity In Vitro"],"prefix":"10.3390","volume":"22","author":[{"given":"Masatoshi","family":"Inden","sequence":"first","affiliation":[{"name":"Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Takagi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazuki","family":"Kitai","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisei","family":"Ito","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisaka","family":"Kurita","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Honda","sequence":"additional","affiliation":[{"name":"The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-5162","authenticated-orcid":false,"given":"Yuji O.","family":"Kamatari","sequence":"additional","affiliation":[{"name":"The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan"},{"name":"Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan"},{"name":"Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sora","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-5171","authenticated-orcid":false,"given":"Xiaopeng","family":"Wen","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-3496","authenticated-orcid":false,"given":"Masanori","family":"Hijioka","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan"},{"name":"Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0984-6291","authenticated-orcid":false,"given":"Isao","family":"Hozumi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Poggiolini, I., Erskine, D., Vaikath, N.N., Ponraj, J., Mansour, S., Morris, C.M., and El-Agnaf, O.M.A. (2021). 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