Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation
Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affec...
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MDPI AG
2024-12-01
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| Series: | Antioxidants |
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| author | Yu-Ling Wu Hai-Lun Sun Jui-Chih Chang Wei-Yong Lin Pei-Yin Chen Chin-Chu Chen Li-Ya Lee Chien-Chun Li Mingli Hsieh Haw-Wen Chen Ya-Chen Yang Chin-San Liu Kai-Li Liu |
| author_facet | Yu-Ling Wu Hai-Lun Sun Jui-Chih Chang Wei-Yong Lin Pei-Yin Chen Chin-Chu Chen Li-Ya Lee Chien-Chun Li Mingli Hsieh Haw-Wen Chen Ya-Chen Yang Chin-San Liu Kai-Li Liu |
| author_sort | Yu-Ling Wu |
| collection | DOAJ |
| description | Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells. Nuclear factor erythroid-derived 2-like 2 (Nrf2), a master transcription factor that controls antioxidant and detoxification gene expression, plays a crucial role in neuroprotection in SCA3 and other neurodegenerative diseases. The present data showed that treatment with erinacine A-enriched <i>Hericium erinaceus</i> mycelium ethanol extract (HEME) extended longevity and improved locomotor activity in ELAV-SCA3tr-Q78 transgenic <i>Drosophila</i>. Moreover, HEME treatment enhanced antioxidant potency and autophagy, which, in turn, corrected levels of mutant polyQ-expanded ataxin-3 and restrained protein aggregation in both cell and <i>Drosophila</i> models of SCA3. Markedly, HEME increased the activation of Nrf2. Silencing Nrf2 protein expression negated most of the promising effects of HEME on SK-N-SH-MJD78 cells, highlighting the critical role of increased Nrf2 activation in the efficacy of HEME treatment. These findings suggest that HEME has therapeutic potential in SCA3 by enhancing autophagic and Nrf2-mediated antioxidant pathways, which may also influence neurodegenerative progression in other polyQ diseases. |
| format | Article |
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| issn | 2076-3921 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Antioxidants |
| spelling | doaj-art-3580a53779ff4ecd89da0c2a1f0401832025-08-20T02:01:01ZengMDPI AGAntioxidants2076-39212024-12-011312149510.3390/antiox13121495Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 ActivationYu-Ling Wu0Hai-Lun Sun1Jui-Chih Chang2Wei-Yong Lin3Pei-Yin Chen4Chin-Chu Chen5Li-Ya Lee6Chien-Chun Li7Mingli Hsieh8Haw-Wen Chen9Ya-Chen Yang10Chin-San Liu11Kai-Li Liu12Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 402, TaiwanCenter of Regenerative Medicine and Tissue Repair, Changhua Christian Hospital, Changhua 500, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, TaiwanDepartment of Senior Citizen Welfare and Long-Term Care Business (Master Program), Hungkuang University, Taichung 433, TaiwanBiotech Research Institute, Grape King Bio Ltd., Taoyuan 325, TaiwanBiotech Research Institute, Grape King Bio Ltd., Taoyuan 325, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung 402, TaiwanDepartment of Life Science and Life Science Research Center, Tunghai University, Taichung 407, TaiwanDepartment of Nutrition, China Medical University, Taichung 404, TaiwanDepartment of Health and Nutrition Biotechnology, Asia University, Taichung 413, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung 402, TaiwanSpinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells. Nuclear factor erythroid-derived 2-like 2 (Nrf2), a master transcription factor that controls antioxidant and detoxification gene expression, plays a crucial role in neuroprotection in SCA3 and other neurodegenerative diseases. The present data showed that treatment with erinacine A-enriched <i>Hericium erinaceus</i> mycelium ethanol extract (HEME) extended longevity and improved locomotor activity in ELAV-SCA3tr-Q78 transgenic <i>Drosophila</i>. Moreover, HEME treatment enhanced antioxidant potency and autophagy, which, in turn, corrected levels of mutant polyQ-expanded ataxin-3 and restrained protein aggregation in both cell and <i>Drosophila</i> models of SCA3. Markedly, HEME increased the activation of Nrf2. Silencing Nrf2 protein expression negated most of the promising effects of HEME on SK-N-SH-MJD78 cells, highlighting the critical role of increased Nrf2 activation in the efficacy of HEME treatment. These findings suggest that HEME has therapeutic potential in SCA3 by enhancing autophagic and Nrf2-mediated antioxidant pathways, which may also influence neurodegenerative progression in other polyQ diseases.https://www.mdpi.com/2076-3921/13/12/1495autophagyerinacine A-enriched <i>Hericium erinaceus</i> myceliummutant polyQ-expanded ataxin-3Nrf2oxidative stressPolyQ diseases |
| spellingShingle | Yu-Ling Wu Hai-Lun Sun Jui-Chih Chang Wei-Yong Lin Pei-Yin Chen Chin-Chu Chen Li-Ya Lee Chien-Chun Li Mingli Hsieh Haw-Wen Chen Ya-Chen Yang Chin-San Liu Kai-Li Liu Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation Antioxidants autophagy erinacine A-enriched <i>Hericium erinaceus</i> mycelium mutant polyQ-expanded ataxin-3 Nrf2 oxidative stress PolyQ diseases |
| title | Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation |
| title_full | Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation |
| title_fullStr | Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation |
| title_full_unstemmed | Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation |
| title_short | Erinacine A-Enriched <i>Hericium erinaceus</i> Mycelium Ethanol Extract Lessens Cellular Damage in Cell and <i>Drosophila</i> Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation |
| title_sort | erinacine a enriched i hericium erinaceus i mycelium ethanol extract lessens cellular damage in cell and i drosophila i models of spinocerebellar ataxia type 3 by improvement of nrf2 activation |
| topic | autophagy erinacine A-enriched <i>Hericium erinaceus</i> mycelium mutant polyQ-expanded ataxin-3 Nrf2 oxidative stress PolyQ diseases |
| url | https://www.mdpi.com/2076-3921/13/12/1495 |
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