Mitoquinone mesylate (Mitoquinone methanesulfonate) is among the widely used antioxidants that target the mitochondria. It was developed to readily penetrate the BBB and neuronal membranes, where it is concentrated into several hundred-folds within the mitochondria where it mediates the local anti-oxidative capacity [1]. Within the ETC, complex II, also known as succinate dehydrogenase, reduces Mitoquinone mesylate ubiquinone moiety to the active antioxidant ubiquinol which scavenges excess ROS [2].
Mitoquinone mesylate (50 nM) reduced 6-OHDA-induced mitochondrial fragmentation, when used in SH-SY5Y cell line. It inhibited mitochondrial fission protein and the translocation of pro-apoptotic protein (Bax) in the mitochondria [3].
Mitoquinone mesylate treatment inhibited the loss of dopaminergic neurons and enhanced behavioral performance, showed neuroprotective effects in mouse models of PD [4]. Mitoquinone mesylate treatment enhanced the fine motor control and reduced markers of oxidative damage in muscles in a Huntington's disease (HD) mouse model [5]. Mitoquinone mesylate reduced white matter injury, improved neurological performance, and decreased motor-evoked potential latency in intracerebral hemorrhagic (ICH) mice [6].
References:
[1]. Murphy M P, Smith R A J. Targeting antioxidants to mitochondria by conjugation to lipophilic cations[J]. Annu. Rev. Pharmacol. Toxicol., 2007, 47: 629-656.
[2]. James A M, Cochemé H M, Smith R A J, et al. Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species: IMPLICATIONS FOR THE USE OF EXOGENOUS UBIQUINONES AS THERAPIES AND EXPERIMENTAL TOOLS. Journal of Biological Chemistry, 2005, 280(22): 21295-21312.
[3]. Solesio M E, Prime T A, Logan A, et al. The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2013, 1832(1): 174-182.
[4]. Pinho B R, Duarte A I, Canas P M, et al. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice[J]. Free Radical Biology and Medicine, 2020, 146: 372-382.
[5]. Pinho B R, Duarte A I, Canas P M, et al. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice[J]. Free Radical Biology and Medicine, 2020, 146: 372-382.
[6]. Chen W, Guo C, Jia Z, et al. Inhibition of mitochondrial ROS by MitoQ alleviates white matter injury and improves outcomes after intracerebral haemorrhage in mice[J]. Oxidative medicine and cellular longevity, 2020, 2020.
Mitoquinone mesylate（Mitoquinone methanesulfonate）是广泛使用的靶向线粒体的抗氧化剂之一。它被开发成很容易穿透 BBB 和神经元膜,在那里它在线粒体中浓缩成数百倍,在线粒体中调节局部抗氧化能力 [1]。在 ETC 中,复合物 II（也称为琥珀酸脱氢酶）将甲磺酸丝裂醌泛醌部分还原为活性抗氧化剂泛醇,后者清除过量的 ROS [2]。
当用于 SH-SY5Y 细胞系时,Mitoquinone mesylate (50 nM) 减少了 6-OHDA 诱导的线粒体断裂。抑制线粒体分裂蛋白和促凋亡蛋白（Bax）在线粒体中的转位[3]。
Mitoquinone mesylate 治疗抑制了多巴胺能神经元的损失并增强了行为表现,在 PD 小鼠模型中显示出神经保护作用 [4]。在亨廷顿舞蹈症 (HD) 小鼠模型中,甲磺酸米托醌治疗增强了精细运动控制并减少了肌肉氧化损伤的标志物[5]。甲磺酸米托醌减少了脑出血 (ICH) 小鼠的白质损伤,改善了神经功能,并减少了运动诱发电位潜伏期 [6]。