摘要
针对许多研究显示高胆固醇与增加患阿尔茨海默病风险性呈正相关,他汀类药物已经被认为是治疗或者预防阿尔茨海默病的替代药物。然而,他汀类药物的潜在益处仍然存在争议性。虽然他汀类药物有降脂的功效,但是它们也有许多与降胆固醇不相关的多种效应,同时具有广泛的生物性意涵,它在大脑中的作用效果还未被充分研究。本文中,我们分析了已报道的他汀类药物在中枢神经系统的有益作用和毒性作用的不同研究,同时查阅了认为其有潜在的治疗阿尔茨海默病的文献。为了解胆固醇水平的改变和AD之间病理学联系提供框架,首先,我们对胆固醇代谢及其在脑内的调节进行了综述。进而我们描述了已报道的他汀类药物在体内和体外模型中的降脂和多效应的功效。我们得出结论,他汀类药物在脑内的作用广泛而复杂,应当仔细分析多效而广泛的他汀类药物治疗包括AD在内的多种疾病的作用。
关键词: 阿尔茨海默病,β淀粉样蛋白,胆固醇通路,HMG-CoA还原酶,类异戊二烯,神经保护作用,神经毒性作用,他汀类
Current Alzheimer Research
Title:The Complex Actions of Statins in Brain and their Relevance for Alzheimer`s Disease Treatment: An Analytical Review
Volume: 11 Issue: 9
Author(s): Ayde Mendoza-Oliva, Angelica Zepeda and Clorinda Arias
Affiliation:
关键词: 阿尔茨海默病,β淀粉样蛋白,胆固醇通路,HMG-CoA还原酶,类异戊二烯,神经保护作用,神经毒性作用,他汀类
摘要: In view that several studies have shown a positive correlation between high cholesterol and an increase in the risk for developing Alzheimer’s disease (AD) statins have been proposed as alternative drugs for its treatment and/or prevention. However, the potential benefits of statins remain controversial. Although they have lipid-lowering properties, statins also have pleiotropic effects that are unrelated to cholesterol reduction and have a wide range of biological implications whose consequences in brain function have not been fully characterized. In this work we analyze different studies that have reported both, beneficial and toxic effects for statins in the central nervous system (CNS), and we revise the literature that claims their potential for treating AD. First, we present an overview of the cholesterol metabolism and its regulation in the brain in order to provide the framework for understanding the pathological association between altered cholesterol and AD. Then, we describe the cholesterol-lowering and pleiotropic properties of statins that have been reported in vivo and in in vitro models. We conclude that the effects of statins in the brain are broad and complex and that their use for treating several diseases including AD should be carefully analyzed given their multiple and broad effects.
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Cite this article as:
Mendoza-Oliva Ayde, Zepeda Angelica and Arias Clorinda, The Complex Actions of Statins in Brain and their Relevance for Alzheimer`s Disease Treatment: An Analytical Review, Current Alzheimer Research 2014; 11 (9) . https://dx.doi.org/10.2174/1567205011666141001114858
DOI https://dx.doi.org/10.2174/1567205011666141001114858 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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