Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain.
Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain.
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DOI：
10.1146/annurev.biochem.78.072407.103859
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发表时间：
2009
影响因子：
16.6
通讯作者：
Kotti T
中科院分区：
文献类型：
--
作者：
Russell DW;Halford RW;Ramirez DM;Shah R;Kotti T
胆固醇 24-羟化酶是一种高度保守的细胞色素 P450，负责脊椎动物中枢神经系统中大部分胆固醇的周转。该酶在神经元中表达，包括对学习和记忆形成很重要的海马和皮质神经元。小鼠胆固醇24-羟化酶基因的破坏会减少大脑中胆固醇的周转和合成，但不会改变组织中胆固醇的稳态水平。合成的下降减少了通过胆固醇生物合成途径的代谢物的流动，其中一种香叶基香叶醇二磷酸是整个动物的学习和体外突触可塑性所必需的。本综述重点关注如何通过实验建立胆固醇代谢与高阶脑功能之间的联系。
Cholesterol 24-hydroxylase is a highly conserved cytochrome P450 that is responsible for the majority of cholesterol turnover in the vertebrate central nervous system. The enzyme is expressed in neurons, including hippocampal and cortical neurons that are important for learning and memory formation. Disruption of the cholesterol 24-hydroxylase gene in the mouse reduces both cholesterol turnover and synthesis in the brain but does not alter steady-state levels of cholesterol in the tissue. The decline in synthesis reduces the flow of metabolites through the cholesterol biosynthetic pathway, of which one, geranylgeraniol diphosphate, is required for learning in the whole animal and for synaptic plasticity in vitro. This review focuses on how the link between cholesterol metabolism and higher-order brain function was experimentally established.
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