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大脑中的胆固醇代谢

Cholesterol metabolism in the brain.

作者信息

Dietschy J M, Turley S D

机构信息

Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-8887, USA.

出版信息

Curr Opin Lipidol. 2001 Apr;12(2):105-12. doi: 10.1097/00041433-200104000-00003.

Abstract

The central nervous system accounts for only 2% of the whole body mass but contains almost a quarter of the unesterified cholesterol present in the whole individual. This sterol is largely present in two pools comprised of the cholesterol in the plasma membranes of glial cells and neurons and the cholesterol present in the specialized membranes of myelin. From 0.02% (human) to 0.4% (mouse) of the cholesterol in these pools turns over each day so that the absolute flux of sterol across the brain is only approximately 0.9% as rapid as the turnover of cholesterol in the whole body of these respective species. The input of cholesterol into the central nervous system comes almost entirely from in situ synthesis, and there is currently little evidence for the net transfer of sterol from the plasma into the brain of the fetus, newborn or adult. In the steady state in the adult, an equivalent amount of cholesterol must move out of the brain and this output is partly accounted for by the formation and excretion of 24S-hydroxycholesterol. This cholesterol turnover across the brain is increased in neurodegenerative disorders such as Alzheimer's disease and Niemann-Pick type C disease. Indirect evidence suggests that large amounts of cholesterol also turn over among the glial cells and neurons within the central nervous system during brain growth and neuron repair and remodelling. This internal recycling of sterol may involve ligands such as apolipoproteins E and AI, and one or more membrane transport proteins such as members of the low density lipoprotein receptor family. Changes in cholesterol balance across the whole body may, in some way, cause alterations in sterol recycling and apolipoprotein E expression within the central nervous system, which, in turn, may affect neuron and myelin integrity. Further elucidation of the processes controlling these events is very important to understand a variety of neurodegenerative disorders.

摘要

中枢神经系统仅占全身质量的2%,但却含有个体全身未酯化胆固醇的近四分之一。这种固醇主要存在于两个池,一个由神经胶质细胞和神经元质膜中的胆固醇组成,另一个由髓鞘特殊膜中的胆固醇组成。这些池中0.02%(人类)至0.4%(小鼠)的胆固醇每天都会更新,因此固醇在大脑中的绝对通量仅约为这些物种全身胆固醇更新速度的0.9%。胆固醇进入中枢神经系统几乎完全来自原位合成,目前几乎没有证据表明固醇能从血浆净转移到胎儿、新生儿或成年人的大脑中。在成年人的稳态下,等量的胆固醇必须从大脑中移出,这种输出部分是由24S - 羟基胆固醇的形成和排泄所导致的。在神经退行性疾病如阿尔茨海默病和尼曼 - 匹克C型病中,大脑中的这种胆固醇更新会增加。间接证据表明,在大脑发育、神经元修复和重塑过程中,大量胆固醇也在中枢神经系统内的神经胶质细胞和神经元之间更新。固醇的这种内部循环可能涉及载脂蛋白E和AI等配体,以及一种或多种膜转运蛋白,如低密度脂蛋白受体家族的成员。全身胆固醇平衡的变化可能会以某种方式导致中枢神经系统内固醇循环和载脂蛋白E表达的改变,进而可能影响神经元和髓鞘的完整性。进一步阐明控制这些事件的过程对于理解各种神经退行性疾病非常重要。

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