Reiss Allison B, Siller Keith A, Rahman Mohammad M, Chan Edwin S L, Ghiso Jorge, de Leon Mony J
Department of Medicine, New York University School of Medicine, New Bellevue 16N1, 550 First Avenue, New York, NY 10016, USA.
Neurobiol Aging. 2004 Sep;25(8):977-89. doi: 10.1016/j.neurobiolaging.2003.11.009.
Mechanisms for the regulation of intracellular cholesterol levels in various types of brain and vascular cells are of considerable importance in our understanding of the pathogenesis of a variety of diseases, particularly atherosclerosis and Alzheimer's disease (AD). It is increasingly clear that conversion of brain cholesterol into 24-hydroxycholesterol and its subsequent release into the periphery is important for the maintenance of brain cholesterol homeostasis. Recent studies have shown elevated plasma concentrations of 24-hydroxycholesterol in patients with AD and vascular dementia, suggesting increased brain cholesterol turnover during neurodegeneration. The oxygenases involved in the degradation and excretion of cholesterol, including the cholesterol 24-hydroxylase and the 27-hydroxylase, are enzymes of the cytochrome P-450 family. This review focuses on the newly recognized importance of cholesterol and its oxygenated metabolites in the pathogenesis of ischemic stroke and AD. The reduction in stroke and AD risk in patients treated with cholesterol-lowering statins is also discussed.
了解各类脑和血管细胞中细胞内胆固醇水平的调节机制，对于我们理解多种疾病（尤其是动脉粥样硬化和阿尔茨海默病（AD））的发病机制具有相当重要的意义。越来越清楚的是，脑胆固醇转化为24-羟基胆固醇并随后释放到外周，对于维持脑胆固醇稳态很重要。最近的研究表明，AD和血管性痴呆患者血浆中24-羟基胆固醇浓度升高，提示神经退行性变期间脑胆固醇周转率增加。参与胆固醇降解和排泄的加氧酶，包括胆固醇24-羟化酶和27-羟化酶，是细胞色素P-450家族的酶。本综述重点关注胆固醇及其氧化代谢产物在缺血性卒中和AD发病机制中新近被认识到的重要性。还讨论了使用降胆固醇他汀类药物治疗的患者中风和AD风险的降低情况。
