Institute of Biomedical Research (BIOMED), Pontifical Catholic University of Argentina (UCA) and National Scientific and Technical Research Council (CONICET), Av. Alicia Moreau de Justo 1600, C1107AFF Buenos Aires, Argentina.
Institute of Biomedical Research (BIOMED), Pontifical Catholic University of Argentina (UCA) and National Scientific and Technical Research Council (CONICET), Av. Alicia Moreau de Justo 1600, C1107AFF Buenos Aires, Argentina.
Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183340. doi: 10.1016/j.bbamem.2020.183340. Epub 2020 May 6.
Starting with cholesterol homeostasis, the first part of the review addresses various aspects of cholesterol metabolism in neuronal and glial cells and the mutual crosstalk between the two cell types, particularly the transport of cholesterol from its site of synthesis to its target loci in neuronal cells, discussing the multiple mechanistic aspects and transporter systems involved. Statins are next analyzed from the point of view of their chemical structure and its impingement on their pharmacological properties and permeability through cell membranes and the blood-brain barrier in particular. The following section then discusses the transcriptional effects of statins and the changes they induce in brain cell genes associated with a variety of processes, including cell growth, signaling and trafficking, uptake and synthesis of cholesterol. We review the effects of statins at the cellular level, analyzing their impact on the cholesterol composition of the nerve and glial cell plasmalemma, neurotransmitter receptor mobilization, myelination, dendritic arborization of neurons, synaptic vesicle release, and cell viability. Finally, the role of statins in disease is exemplified by Alzheimer and Parkinson diseases and some forms of epilepsy, both in animal models and in the human form of these pathologies.
从胆固醇稳态开始，这篇综述的第一部分讨论了神经元和神经胶质细胞中胆固醇代谢的各个方面以及这两种细胞类型之间的相互交流，特别是胆固醇从合成部位向神经元细胞靶位的运输，讨论了涉及的多种机制方面和转运体系统。接下来，从化学结构的角度分析他汀类药物及其对其药理特性和通过细胞膜特别是血脑屏障通透性的影响。接下来的一节讨论了他汀类药物的转录效应及其在与多种过程相关的脑细胞基因中诱导的变化，包括细胞生长、信号转导和运输、胆固醇的摄取和合成。我们在细胞水平上研究了他汀类药物的作用，分析了它们对神经和神经胶质细胞膜胆固醇组成、神经递质受体动员、髓鞘形成、神经元树突分支、突触小泡释放和细胞活力的影响。最后，以阿尔茨海默病和帕金森病以及某些形式的癫痫为例，说明了他汀类药物在疾病中的作用，包括在动物模型和这些病理的人类形式中。
