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Article

1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis

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Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8520, Japan
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Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8520, Japan
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Department of Physiology, Division of Brain Science, Kurume University School of Medicine, Kurume 830-0011, Japan
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Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8520, Japan
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Department of Pharmacology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8544, Japan
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Laboratory of Functional Foods, Department of Biomedical Engineering, Osaka Institute of Technology, Osaka 535-8585, Japan
*
Authors to whom correspondence should be addressed.
Academic Editors: Kazuhide Hayakawa and Melitta Schachner
Int. J. Mol. Sci. 2021, 22(18), 9941; https://doi.org/10.3390/ijms22189941
Received: 25 August 2021 / Revised: 8 September 2021 / Accepted: 10 September 2021 / Published: 14 September 2021
(This article belongs to the Special Issue Mitochondrial Function in Neurodegenerative Diseases)
Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson’s disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD. View Full-Text
Keywords: 1,5-AF; 1,5-AG; metformin; Parkinson’s disease; parkinsonism; AMPK; PGC-1α; mitochondria; mitochondrial biogenesis; rotenone 1,5-AF; 1,5-AG; metformin; Parkinson’s disease; parkinsonism; AMPK; PGC-1α; mitochondria; mitochondrial biogenesis; rotenone
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MDPI and ACS Style

Kasamo, Y.; Kikuchi, K.; Yamakuchi, M.; Otsuka, S.; Takada, S.; Kambe, Y.; Ito, T.; Kawahara, K.-i.; Arita, K.; Yoshimoto, K.; Maruyama, I. 1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis. Int. J. Mol. Sci. 2021, 22, 9941. https://doi.org/10.3390/ijms22189941

AMA Style

Kasamo Y, Kikuchi K, Yamakuchi M, Otsuka S, Takada S, Kambe Y, Ito T, Kawahara K-i, Arita K, Yoshimoto K, Maruyama I. 1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis. International Journal of Molecular Sciences. 2021; 22(18):9941. https://doi.org/10.3390/ijms22189941

Chicago/Turabian Style

Kasamo, Yuki, Kiyoshi Kikuchi, Munekazu Yamakuchi, Shotaro Otsuka, Seiya Takada, Yuki Kambe, Takashi Ito, Ko-ichi Kawahara, Kazunori Arita, Koji Yoshimoto, and Ikuro Maruyama. 2021. "1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis" International Journal of Molecular Sciences 22, no. 18: 9941. https://doi.org/10.3390/ijms22189941

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