Yang Lichuan, Calingasan Noel Y, Wille Elizabeth J, Cormier Kerry, Smith Karen, Ferrante Robert J, Beal M Flint
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA.
J Neurochem. 2009 Jun;109(5):1427-39. doi: 10.1111/j.1471-4159.2009.06074.x. Epub 2009 Mar 28.
Coenzyme Q(10) (CoQ(10)) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ(10) with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic alpha-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ(10) and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD.
辅酶Q(10)（CoQ(10)）和肌酸有望通过改善线粒体功能和细胞生物能量代谢以及作为抗氧化剂的特性，对神经退行性疾病起到神经保护作用。我们研究了CoQ(10)与肌酸联合使用是否能在帕金森病的MPTP小鼠模型、亨廷顿舞蹈病（HD）的3-NP大鼠模型以及HD的R6/2转基因小鼠模型中发挥额外的神经保护作用。在慢性皮下注射MPTP后，这两种药物的联合使用对纹状体多巴胺耗竭和黑质致密部（SNpc）酪氨酸羟化酶神经元的丧失产生了额外的神经保护作用。联合治疗使MPTP处理小鼠的SNpc神经元中的脂质过氧化和病理性α-突触核蛋白积累显著减少。我们还观察到，在减少慢性皮下注射3-NP给大鼠所产生的纹状体损伤体积方面，联合治疗具有额外的神经保护作用。联合治疗对阻止3-NP诱导的谷胱甘肽稳态受损以及减少纹状体中的脂质过氧化和DNA氧化损伤具有显著作用。最后，CoQ(10)和肌酸的联合使用对改善转基因R6/2 HD小鼠的运动性能和延长生存期产生了额外的神经保护作用。这些发现表明，使用CoQ(10)和肌酸的联合疗法可能对治疗帕金森病和HD等神经退行性疾病有用。
