SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease
Epidemiological studies have linked herbicides and Parkinson's disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722003068 |
| _version_ | 1811207051592859648 |
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| author | Chih-Chang Chao Chuen-Lin Huang Jing-Jy Cheng Chun-Tang Chiou I-Jung Lee Ying-Chen Yang Ting-Huang Hsu Chia-En Yei Pei-Ying Lin Jih-Jung Chen Nai-Kuei Huang |
| author_facet | Chih-Chang Chao Chuen-Lin Huang Jing-Jy Cheng Chun-Tang Chiou I-Jung Lee Ying-Chen Yang Ting-Huang Hsu Chia-En Yei Pei-Ying Lin Jih-Jung Chen Nai-Kuei Huang |
| author_sort | Chih-Chang Chao |
| collection | DOAJ |
| description | Epidemiological studies have linked herbicides and Parkinson's disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1 synthesized by Sirtris, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720's protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1α and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD. |
| first_indexed | 2024-04-12T03:58:35Z |
| format | Article |
| id | doaj.art-a5bd6a275cd94268b734a16789761737 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T03:58:35Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-a5bd6a275cd94268b734a167897617372022-12-22T03:48:46ZengElsevierRedox Biology2213-23172022-12-0158102534SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's diseaseChih-Chang Chao0Chuen-Lin Huang1Jing-Jy Cheng2Chun-Tang Chiou3I-Jung Lee4Ying-Chen Yang5Ting-Huang Hsu6Chia-En Yei7Pei-Ying Lin8Jih-Jung Chen9Nai-Kuei Huang10Institute of Neuroscience, National Chengchi University, Taipei, TaiwanMedical Research Center, Cardinal Tien Hospital, Hsintien, New Taipei City, Taiwan; Graduate Institute of Physiology & Department of Physiology and Biophysics, National Defense Medical Center, Taipei, 114, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, 112, Taiwan; Institute of Biophotonics, National Yang-Ming University, Taipei, 112, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, 112, TaiwanHerbal Medicine Department, Yokohama University of Pharmacy, Yokohama, JapanDepartment of Biotechnology and Animal Science, National Ilan University, Ilan, TaiwanInstitute of Neuroscience, National Chengchi University, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, 112, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, 112, TaiwanDepartment of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan; Department of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming Chiao Tung University, Taipei 112304, Taiwan; Corresponding author. National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No.155, Li-Nung St., Sec. 2, Shipai, Peitou, Taipei, 112, Taiwan.National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, 112, Taiwan; Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan; Corresponding author. School of Pharmaceutical Sciences, National Yang-Ming Chiao Tung University, No. 155-1 Li-Nung St., Sec. 2, Shipai, Peitou, Taipei, 112, Taiwan.Epidemiological studies have linked herbicides and Parkinson's disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1 synthesized by Sirtris, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720's protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1α and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD.http://www.sciencedirect.com/science/article/pii/S2213231722003068Sirtuin1SRT1720MitochondriaParaquatParkinson's disease |
| spellingShingle | Chih-Chang Chao Chuen-Lin Huang Jing-Jy Cheng Chun-Tang Chiou I-Jung Lee Ying-Chen Yang Ting-Huang Hsu Chia-En Yei Pei-Ying Lin Jih-Jung Chen Nai-Kuei Huang SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease Redox Biology Sirtuin1 SRT1720 Mitochondria Paraquat Parkinson's disease |
| title | SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease |
| title_full | SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease |
| title_fullStr | SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease |
| title_full_unstemmed | SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease |
| title_short | SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease |
| title_sort | srt1720 as an sirt1 activator for alleviating paraquat induced models of parkinson s disease |
| topic | Sirtuin1 SRT1720 Mitochondria Paraquat Parkinson's disease |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722003068 |
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