Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Ann N Y Acad Sci. 2010 Jun;1199:69-76. doi: 10.1111/j.1749-6632.2009.05359.x.
There is growing interest in the use of statins, HMG-CoA reductase inhibitors, for treating specific neurodegenerative diseases (e.g., cerebrovascular disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis) and possibly traumatic brain injury. Neither is there a consensus on the efficacy of statins in treating the aforementioned diseases nor are the mechanisms of the purported statin-induced neuroprotection well-understood. Part of the support for statin-induced neuroprotection comes from studies using animal models and cell culture. Important information has resulted from that work but there continues to be a lack of progress on basic issues pertaining to statins and brain that impedes advancement in understanding how statins alter brain function. For example, there are scant data on the pharmacokinetics of lipophilic and hydrophilic statins in brain, statin-induced neuroprotection versus cell death, and statins and brain isoprenoids. The purpose of this mini-review will be to examine those aforementioned issues and to identify directions of future research.
人们对他汀类药物(HMG-CoA 还原酶抑制剂)在治疗特定神经退行性疾病(如脑血管病、帕金森病、阿尔茨海默病、多发性硬化症)和可能的创伤性脑损伤中的应用越来越感兴趣。目前对于他汀类药物治疗上述疾病的疗效尚无共识,也不清楚所谓的他汀类药物诱导的神经保护作用的机制。他汀类药物诱导神经保护的部分支持来自于动物模型和细胞培养的研究。这些工作产生了重要信息,但在与他汀类药物和大脑相关的基本问题上仍缺乏进展,这阻碍了人们对他汀类药物如何改变大脑功能的理解。例如,关于亲脂性和亲水性他汀类药物在大脑中的药代动力学、他汀类药物诱导的神经保护与细胞死亡以及他汀类药物和大脑异戊二烯的相关数据很少。本文的主要目的将是检查上述问题,并确定未来研究的方向。