Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases
Yue Zhang,1,2,* Meiyan Sun,2,* Hongxiang Zhao,1,2,* Zhengyan Wang,2 Yanan Shi,2 Jianxin Dong,2 Kaifang Wang,3 Xi Wang,4 Xingyue Li,5 Haiyan Qi,6 Xiaoyong Zhao1,2,7 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer...
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Dove Medical Press
2023-12-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/neuroprotective-effects-and-therapeutic-potential-of-dichloroacetate-t-peer-reviewed-fulltext-article-IJN |
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| author | Zhang Y Sun M Zhao H Wang Z Shi Y Dong J Wang K Wang X Li X Qi H Zhao X |
| author_facet | Zhang Y Sun M Zhao H Wang Z Shi Y Dong J Wang K Wang X Li X Qi H Zhao X |
| author_sort | Zhang Y |
| collection | DOAJ |
| description | Yue Zhang,1,2,* Meiyan Sun,2,* Hongxiang Zhao,1,2,* Zhengyan Wang,2 Yanan Shi,2 Jianxin Dong,2 Kaifang Wang,3 Xi Wang,4 Xingyue Li,5 Haiyan Qi,6 Xiaoyong Zhao1,2,7 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 3Department of Anesthesia, Tangdu Hospital, Fourth Military Medical University, Xian, Shanxi Province, People’s Republic of China; 4Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 6Department of Anesthesiology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 7Department of Anesthesiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyong Zhao; Haiyan Qi, Email xyzhao83@163.com; qihy123@163.comAbstract: Dichloroacetate (DCA) is an investigational drug used to treat lactic acidosis and malignant tumours. It works by inhibiting pyruvate dehydrogenase kinase and increasing the rate of glucose oxidation. Some studies have documented the neuroprotective benefits of DCA. By reviewing these studies, this paper shows that DCA has multiple pharmacological activities, including regulating metabolism, ameliorating oxidative stress, attenuating neuroinflammation, inhibiting apoptosis, decreasing autophagy, protecting the blood‒brain barrier, improving the function of endothelial progenitor cells, improving mitochondrial dynamics, and decreasing amyloid β-protein. In addition, DCA inhibits the enzyme that metabolizes it, which leads to peripheral neurotoxicity due to drug accumulation that may be solved by individualized drug delivery and nanovesicle delivery. In summary, in this review, we analyse the mechanisms of neuroprotection by DCA in different diseases and discuss the causes of and solutions to its adverse effects.Keywords: dichloroacetate, neuroprotection, mitochondria, energy metabolism, oxidative stress |
| first_indexed | 2024-03-08T23:28:58Z |
| format | Article |
| id | doaj.art-845971a300f845bba4220fca20a310ef |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-03-08T23:28:58Z |
| publishDate | 2023-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-845971a300f845bba4220fca20a310ef2023-12-14T17:01:44ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-12-01Volume 187559758188955Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System DiseasesZhang YSun MZhao HWang ZShi YDong JWang KWang XLi XQi HZhao XYue Zhang,1,2,* Meiyan Sun,2,* Hongxiang Zhao,1,2,* Zhengyan Wang,2 Yanan Shi,2 Jianxin Dong,2 Kaifang Wang,3 Xi Wang,4 Xingyue Li,5 Haiyan Qi,6 Xiaoyong Zhao1,2,7 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 3Department of Anesthesia, Tangdu Hospital, Fourth Military Medical University, Xian, Shanxi Province, People’s Republic of China; 4Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 6Department of Anesthesiology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 7Department of Anesthesiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyong Zhao; Haiyan Qi, Email xyzhao83@163.com; qihy123@163.comAbstract: Dichloroacetate (DCA) is an investigational drug used to treat lactic acidosis and malignant tumours. It works by inhibiting pyruvate dehydrogenase kinase and increasing the rate of glucose oxidation. Some studies have documented the neuroprotective benefits of DCA. By reviewing these studies, this paper shows that DCA has multiple pharmacological activities, including regulating metabolism, ameliorating oxidative stress, attenuating neuroinflammation, inhibiting apoptosis, decreasing autophagy, protecting the blood‒brain barrier, improving the function of endothelial progenitor cells, improving mitochondrial dynamics, and decreasing amyloid β-protein. In addition, DCA inhibits the enzyme that metabolizes it, which leads to peripheral neurotoxicity due to drug accumulation that may be solved by individualized drug delivery and nanovesicle delivery. In summary, in this review, we analyse the mechanisms of neuroprotection by DCA in different diseases and discuss the causes of and solutions to its adverse effects.Keywords: dichloroacetate, neuroprotection, mitochondria, energy metabolism, oxidative stresshttps://www.dovepress.com/neuroprotective-effects-and-therapeutic-potential-of-dichloroacetate-t-peer-reviewed-fulltext-article-IJNdichloroacetateneuroprotectionmitochondriaenergy metabolismoxidative stress |
| spellingShingle | Zhang Y Sun M Zhao H Wang Z Shi Y Dong J Wang K Wang X Li X Qi H Zhao X Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases International Journal of Nanomedicine dichloroacetate neuroprotection mitochondria energy metabolism oxidative stress |
| title | Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases |
| title_full | Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases |
| title_fullStr | Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases |
| title_full_unstemmed | Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases |
| title_short | Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases |
| title_sort | neuroprotective effects and therapeutic potential of dichloroacetate targeting metabolic disorders in nervous system diseases |
| topic | dichloroacetate neuroprotection mitochondria energy metabolism oxidative stress |
| url | https://www.dovepress.com/neuroprotective-effects-and-therapeutic-potential-of-dichloroacetate-t-peer-reviewed-fulltext-article-IJN |
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