{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:52:30Z","timestamp":1785307950610,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"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":["16K08276"],"award-info":[{"award-number":["16K08276"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K07123"],"award-info":[{"award-number":["19K07123"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Joint Research Program of the Biosignal Research Center, Kobe University","award":["281007"],"award-info":[{"award-number":["281007"]}]},{"name":"The Joint Research Program of the Biosignal Research Center, Kobe University","award":["191005"],"award-info":[{"award-number":["191005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The inflammatory activation of microglia participates in dopaminergic neurodegeneration in PD. Therefore, chemicals that inhibit microglial activation are considered to have therapeutic potential for PD. Aromatic (ar)-turmerone is a main component of turmeric oil extracted from Curcuma longa and has anti-inflammatory activity in cultured microglia. The aims of the present study are (1) to investigate whether naturally occurring S-enantiomer of ar-turmerone (S-Tur) protects dopaminergic neurons in midbrain slice cultures and (2) to examine ar-turmerone analogs that have higher activities than S-Tur in inhibiting microglial activation and protecting dopaminergic neurons. R-enantiomer (R-Tur) and two analogs showed slightly higher anti-inflammatory effects in microglial BV2 cells. S- and R-Tur and these two analogs reversed dopaminergic neurodegeneration triggered by microglial activation in midbrain slice cultures. Unexpectedly, this neuroprotection was independent of the inhibition of microglial activation. Additionally, two analogs more potently inhibited dopaminergic neurodegeneration triggered by a neurotoxin, 1-methyl-4-phenylpyridinium, than S-Tur. Taken together, we identified two ar-turmerone analogs that directly and potently protected dopaminergic neurons. An investigation using dopaminergic neuronal precursor cells suggested the possible involvement of nuclear factor erythroid 2-related factor 2 in this neuroprotection.<\/jats:p>","DOI":"10.3390\/cells10051090","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T11:06:01Z","timestamp":1620212761000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities"],"prefix":"10.3390","volume":"10","author":[{"given":"Yuria","family":"Hori","sequence":"first","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiho","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Nasu","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-6452","authenticated-orcid":false,"given":"Alex","family":"Boateng","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Ashikari","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan"},{"name":"Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kurauchi","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Hisatsune","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7595-3154","authenticated-orcid":false,"given":"Hiroshi","family":"Katsuki","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1602\/neurorx.1.1.139","article-title":"Neurodegeneration and Neuroprotection in Parkinson Disease","volume":"1","author":"Fahn","year":"2004","journal-title":"NeuroRx"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/hmg\/ddm159","article-title":"Parkinson\u2019s disease","volume":"16","author":"Thomas","year":"2007","journal-title":"Hum. 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