Tarnopolsky M A, Beal M F
Department of Neurology, McMaster University, Hamilton, Ontario, Canada.
Ann Neurol. 2001 May;49(5):561-74.
Substantial evidence indicates that bioenergetic dysfunction plays either a primary or secondary role in the pathophysiology of cell death in neurodegenerative and neuromuscular disorders, and even in normal aging. Agents that ameliorate bioenergetic defects may therefore be useful in therapy. Creatine, which increases muscle and brain phosphocreatine concentrations, and may inhibit the activation of the mitochondrial permeability transition, protects against neuronal degeneration in transgenic murine models of amyotrophic lateral sclerosis and Huntington's disease and in chemically mediated neurotoxicity. Initial studies of creatine use in humans appear promising; however, further long-term, well-designed trials are needed. Coenzyme Q10, Gingko biloba, nicotinamide, riboflavin, carnitine, lipoic acid, and dichloroacetate are other agents which may have beneficial effects on energy metabolism, but the preclinical and clinical evidence for efficacy in neurological diseases remains limited. These compounds are widely used as dietary supplements; however, they must be subjected to rigorous evaluation through randomized, double-blinded trials to establish efficacy, cost-effectiveness and safety in neurological disorders.
大量证据表明，生物能量功能障碍在神经退行性疾病、神经肌肉疾病甚至正常衰老过程中的细胞死亡病理生理学中起着主要或次要作用。因此，改善生物能量缺陷的药物可能对治疗有用。肌酸可增加肌肉和大脑中磷酸肌酸的浓度，并可能抑制线粒体通透性转换的激活，在肌萎缩侧索硬化症和亨廷顿舞蹈症的转基因小鼠模型以及化学介导的神经毒性中可防止神经元变性。对人类使用肌酸的初步研究似乎很有前景；然而，还需要进一步进行长期的、精心设计的试验。辅酶Q10、银杏叶、烟酰胺、核黄素、肉碱、硫辛酸和二氯乙酸是其他可能对能量代谢有有益作用的药物，但在神经疾病中疗效的临床前和临床证据仍然有限。这些化合物被广泛用作膳食补充剂；然而，必须通过随机双盲试验对它们进行严格评估，以确定其在神经疾病中的疗效、成本效益和安全性。
