Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease
Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson’s disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (M...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1363212/full |
| _version_ | 1797294171922366464 |
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| author | Qing-Wei Ma Rui-Ting Han Zi-Jie Wu Jun-Jie Zhou Meng-Ting Chen Xiang-Zhi Zhang Wen-Zhe Ma Na Feng |
| author_facet | Qing-Wei Ma Rui-Ting Han Zi-Jie Wu Jun-Jie Zhou Meng-Ting Chen Xiang-Zhi Zhang Wen-Zhe Ma Na Feng |
| author_sort | Qing-Wei Ma |
| collection | DOAJ |
| description | Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson’s disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces α-synuclein aggregation in Caenorhabditis elegans; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson’s disease. |
| first_indexed | 2024-03-07T21:26:23Z |
| format | Article |
| id | doaj.art-f3b02285f95c4729978a13f1299f7998 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-07T21:26:23Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f3b02285f95c4729978a13f1299f79982024-02-27T04:57:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-02-011510.3389/fphar.2024.13632121363212Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s diseaseQing-Wei Ma0Rui-Ting Han1Zi-Jie Wu2Jun-Jie Zhou3Meng-Ting Chen4Xiang-Zhi Zhang5Wen-Zhe Ma6Na Feng7School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, ChinaSchool of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaBoth continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson’s disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces α-synuclein aggregation in Caenorhabditis elegans; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson’s disease.https://www.frontiersin.org/articles/10.3389/fphar.2024.1363212/fullmelatonin derivativeParkinson’s diseasePARP-1mTORmitochondrial dysfunction |
| spellingShingle | Qing-Wei Ma Rui-Ting Han Zi-Jie Wu Jun-Jie Zhou Meng-Ting Chen Xiang-Zhi Zhang Wen-Zhe Ma Na Feng Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease Frontiers in Pharmacology melatonin derivative Parkinson’s disease PARP-1 mTOR mitochondrial dysfunction |
| title | Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease |
| title_full | Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease |
| title_fullStr | Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease |
| title_full_unstemmed | Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease |
| title_short | Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease |
| title_sort | melatonin derivative 6a as a parp 1 inhibitor for the treatment of parkinson s disease |
| topic | melatonin derivative Parkinson’s disease PARP-1 mTOR mitochondrial dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1363212/full |
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