CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI), 67084 Strasbourg Cedex, France.
Prog Lipid Res. 2011 Oct;50(4):357-71. doi: 10.1016/j.plipres.2011.06.002. Epub 2011 Jul 1.
Cells in the mammalian body must accurately maintain their content of cholesterol, which is an essential membrane component and precursor for vital signalling molecules. Outside the brain, cholesterol homeostasis is guaranteed by a lipoprotein shuttle between the liver, intestine and other organs via the blood circulation. Cells inside the brain are cut off from this circuit by the blood-brain barrier and must regulate their cholesterol content in a different manner. Here, we review how this is accomplished by neurons and astrocytes, two cell types of the central nervous system, whose cooperation is essential for normal brain development and function. The key observation is a remarkable cell-specific distribution of proteins that mediate different steps of cholesterol metabolism. This form of metabolic compartmentalization identifies astrocytes as net producers of cholesterol and neurons as consumers with unique means to prevent cholesterol overload. The idea that cholesterol turnover in neurons depends on close cooperation with astrocytes raises new questions that need to be addressed by new experimental approaches to monitor and manipulate cholesterol homeostasis in a cell-specific manner. We conclude that an understanding of cholesterol metabolism in the brain and its role in disease requires a close look at individual cell types.
哺乳动物体内的细胞必须准确维持胆固醇的含量，胆固醇是膜的重要组成部分，也是重要信号分子的前体。在大脑之外，胆固醇的动态平衡是通过脂蛋白在肝脏、肠道和其他器官之间通过血液循环进行的穿梭来保证的。大脑内的细胞被血脑屏障隔开，必须以不同的方式调节其胆固醇含量。在这里，我们回顾了神经元和星形胶质细胞（中枢神经系统的两种细胞类型）如何实现这一点，它们的合作对于正常的大脑发育和功能至关重要。关键的观察结果是介导胆固醇代谢不同步骤的蛋白质具有显著的细胞特异性分布。这种代谢区室化形式将星形胶质细胞鉴定为胆固醇的净生产者，而神经元则具有独特的手段来防止胆固醇过载，作为胆固醇的消费者。神经元中胆固醇周转率取决于与星形胶质细胞的紧密合作，这一观点提出了新的问题，需要通过新的实验方法来解决，以特定于细胞的方式监测和操纵胆固醇动态平衡。我们的结论是，要理解大脑中的胆固醇代谢及其在疾病中的作用，需要仔细观察单个细胞类型。
