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Article

Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities

by
Yuria Hori
1,
Reiho Tsutsumi
1,
Kento Nasu
1,
Alex Boateng
2,
Yasuhiko Ashikari
3,
Masaharu Sugiura
2,3,
Makoto Nakajima
3,
Yuki Kurauchi
1,
Akinori Hisatsune
1,
Hiroshi Katsuki
1 and
Takahiro Seki
1,*
1
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan
2
Graduate School of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan
3
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan
*
Author to whom correspondence should be addressed.
Cells 2021, 10(5), 1090; https://doi.org/10.3390/cells10051090
Submission received: 15 March 2021 / Revised: 30 April 2021 / Accepted: 1 May 2021 / Published: 3 May 2021
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Japan)
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Abstract

Parkinson’s 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.
Keywords: aromatic-turmerone; dopaminergic neurons; microglia; Nrf2 aromatic-turmerone; dopaminergic neurons; microglia; Nrf2

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MDPI and ACS Style

Hori, Y.; Tsutsumi, R.; Nasu, K.; Boateng, A.; Ashikari, Y.; Sugiura, M.; Nakajima, M.; Kurauchi, Y.; Hisatsune, A.; Katsuki, H.; et al. Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities. Cells 2021, 10, 1090. https://doi.org/10.3390/cells10051090

AMA Style

Hori Y, Tsutsumi R, Nasu K, Boateng A, Ashikari Y, Sugiura M, Nakajima M, Kurauchi Y, Hisatsune A, Katsuki H, et al. Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities. Cells. 2021; 10(5):1090. https://doi.org/10.3390/cells10051090

Chicago/Turabian Style

Hori, Yuria, Reiho Tsutsumi, Kento Nasu, Alex Boateng, Yasuhiko Ashikari, Masaharu Sugiura, Makoto Nakajima, Yuki Kurauchi, Akinori Hisatsune, Hiroshi Katsuki, and et al. 2021. "Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities" Cells 10, no. 5: 1090. https://doi.org/10.3390/cells10051090

APA Style

Hori, Y., Tsutsumi, R., Nasu, K., Boateng, A., Ashikari, Y., Sugiura, M., Nakajima, M., Kurauchi, Y., Hisatsune, A., Katsuki, H., & Seki, T. (2021). Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities. Cells, 10(5), 1090. https://doi.org/10.3390/cells10051090

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