Baker Steven K, Tarnopolsky Mark A
Neurology and Rehabilitation, Room 4U4, Department of Medicine, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada.
Expert Opin Investig Drugs. 2003 Oct;12(10):1655-79. doi: 10.1517/13543784.12.10.1655.
The concepts of energy dysregulation and oxidative stress and their complicated interdependence have rapidly evolved to assume primary importance in understanding the pathophysiology of numerous neurological disorders. Therefore, neuroprotective strategies addressing specific bioenergetic defects hold particular promise in the treatment of these conditions (i.e., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Friedreich's ataxia, mitochondrial cytopathies and other neuromuscular diseases), all of which, to some extent, share 'the final common pathway' leading to cell death through either necrosis or apoptosis. Compounds such as creatine monohydrate and coenzyme Q(10) offer substantial neuroprotection against ischaemia, trauma, oxidative damage and neurotoxins. Miscellaneous agents, including alpha-lipoic acid, beta-OH-beta-methylbutyrate, riboflavin and nicotinamide, have also been shown to improve various metabolic parameters in brain and/or muscle. This review will highlight the biological function of each of the above mentioned compounds followed by a discussion of their utility in animal models and human neurological disease. The balance of this work will be comprised of discussions on the therapeutic applications of creatine and coenzyme Q(10).
能量调节异常和氧化应激的概念及其复杂的相互依存关系已迅速发展，在理解众多神经疾病的病理生理学方面占据了首要地位。因此，针对特定生物能量缺陷的神经保护策略在治疗这些疾病（即肌萎缩侧索硬化症、亨廷顿舞蹈症、帕金森病、弗里德赖希共济失调、线粒体细胞病及其他神经肌肉疾病）方面具有特别的前景，所有这些疾病在某种程度上都共享通过坏死或凋亡导致细胞死亡的“最终共同途径”。诸如一水肌酸和辅酶Q10等化合物对缺血、创伤、氧化损伤和神经毒素具有显著的神经保护作用。其他一些药物，包括α-硫辛酸、β-羟基-β-甲基丁酸、核黄素和烟酰胺，也已被证明可改善大脑和/或肌肉中的各种代谢参数。本综述将重点介绍上述每种化合物的生物学功能，随后讨论它们在动物模型和人类神经疾病中的效用。本文的其余部分将围绕肌酸和辅酶Q10的治疗应用展开讨论。
