Willey Joshua Z, Elkind Mitchell S V
Department of Neurology, Columbia University, New York, NY 10032, USA.
Arch Neurol. 2010 Sep;67(9):1062-7. doi: 10.1001/archneurol.2010.199.
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are among the most prescribed medications in the United States. Statins act on the rate-limiting step in cholesterol biosynthesis (the conversion of HMG-CoA to mevalonate) and are effective in treating dyslipidemia. However, statins decrease other downstream products of the mevalonate pathway, and it is via these pathways that statins may affect inflammation, nitric oxide synthesis, the coagulation cascade, and other processes. Through these pleiotropic effects, statins may have an effect on neurologic diseases, including ischemic and hemorrhagic stroke, Alzheimer disease, Parkinson disease, and multiple sclerosis. This article reviews the basic biochemistry of statins as it relates to these pleiotropic effects, the potential role of statins in several neurologic disorders, and the results of clinical trials performed for several of these conditions.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）是美国处方量最大的药物之一。他汀类药物作用于胆固醇生物合成的限速步骤（HMG-CoA转化为甲羟戊酸），对治疗血脂异常有效。然而，他汀类药物会减少甲羟戊酸途径的其他下游产物，而他汀类药物正是通过这些途径可能影响炎症、一氧化氮合成、凝血级联反应及其他过程。通过这些多效性作用，他汀类药物可能对包括缺血性和出血性中风、阿尔茨海默病、帕金森病及多发性硬化症在内的神经系统疾病产生影响。本文综述了与这些多效性作用相关的他汀类药物的基础生物化学、他汀类药物在几种神经系统疾病中的潜在作用，以及针对其中几种病症所进行的临床试验结果。
