Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases

被引:4
|
作者
Zhang, Yue [1 ,2 ,3 ]
Sun, Meiyan [3 ]
Zhao, Hongxiang [1 ,2 ,3 ]
Wang, Zhengyan [3 ]
Shi, Yanan [3 ]
Dong, Jianxin [3 ]
Wang, Kaifang [4 ]
Wang, Xi [5 ]
Li, Xingyue [6 ]
Qi, Haiyan [7 ]
Zhao, Xiaoyong [1 ,2 ,3 ,8 ]
机构
[1] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Radiat Oncol, Jinan, Shandong, Peoples R China
[2] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Shandong Prov Key Lab Radiat Oncol, Jinan, Shandong, Peoples R China
[3] Weifang Med Univ, Sch Anesthesiol, Lab Anesthesia & Crit Care Med Coll & Univ Shandon, Weifang, Shandong, Peoples R China
[4] Fourth Mil Med Univ, Tangdu Hosp, Dept Anesthesia, Xian, Shanxi, Peoples R China
[5] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Anesthesiol, Hangzhou, Zhejiang, Peoples R China
[6] Weifang Med Univ, Affiliated Hosp, Dept Hepatobiliary & Pancreat Surg, Weifang, Shandong, Peoples R China
[7] Shandong First Med Univ, Jinan Matern & Child Care Hosp, Dept Anesthesiol, Jinan, Shandong, Peoples R China
[8] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Anesthesiol, Jinan, Shandong, Peoples R China
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2023年 / 18卷
关键词
dichloroacetate; neuroprotection; mitochondria; energy metabolism; oxidative stress; GLUTATHIONE-TRANSFERASE-ZETA; PYRUVATE-DEHYDROGENASE ACTIVITY; CONGENITAL LACTIC-ACIDOSIS; ELECTRON-TRANSPORT CHAIN; DRUG-DELIVERY SYSTEM; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; SKELETAL-MUSCLE; ISCHEMIA-REPERFUSION; HAPLOTYPE VARIATIONS;
D O I
10.2147/IJN.S439728
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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 beta-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.
引用
收藏
页码:7559 / 7581
页数:23
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