Cholesterol and Amyloid-β: Evidence for a Cross-Talk between Astrocytes and Neuronal Cells
Cholesterol and Amyloid-β: Evidence for a Cross-Talk between Astrocytes and Neuronal Cells
复制标题
DOI：
10.3233/jad-2011-110053
复制
发表时间：
2011-01-01
影响因子：
4
通讯作者：
Ricciarelli, Roberta
中科院分区：
文献类型：
--
作者：
Canepa, Elisa;Borghi, Roberta;Ricciarelli, Roberta
越来越多的数据支持这样一个概念，即胆固醇代谢的变化可能会影响阿尔茨海默病(AD)的发展，AD是一种神经退行性疾病，其特征是淀粉样β蛋白(Aβ)多肽在大脑中逐渐积聚。神经元产生Aβ的变化被描述为胆固醇水平的函数，因此表明胆固醇稳态失调与AD发病之间存在因果联系。在生理条件下，大脑中的胆固醇摄取被血脑屏障有效地阻止，成熟的神经元被认为依赖神经胶质细胞提供胆固醇。在目前的研究中，我们验证了这样的假设，即Aβ可能作为一种信号分子，能够向星形胶质网络告知神经元对胆固醇的需求。总而言之，我们的数据支持这一假设，并首次证明，Aβ(42)对培养的星形胶质细胞中胆固醇转运体ABCA1的表达具有抑制作用。相应地，我们还发现在AβPP/PS1转基因小鼠的大脑中ABCA1的表达减少。这些结果为Aβ多肽提供了生物学功能，并可能有助于确定脑内胆固醇代谢与AD之间的致病关系。
Accumulating data support the concept that alterations of cholesterol metabolism might influence the development of Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive accumulation of amyloid-beta (A beta) peptides in the brain. Changes in the neuronal production of A beta have been described as a function of cholesterol levels, thus suggesting a causal link between cholesterol homeostasis dysregulation and AD pathogenesis. Under physiological conditions, cholesterol uptake in the brain is efficiently prevented by the blood-brain barrier, and mature neurons are thought to rely on glial cells for their cholesterol supply. In the present study, we tested the hypothesis that A beta may serve as a signaling molecule capable of informing the astroglial network about the neuronal need for cholesterol. Collectively, our data bolster this hypothesis and demonstrate, for the first time, that A beta(42) exerts an inhibitory effect on the expression of the cholesterol transporter ABCA1 in cultured astrocytes. Accordingly, we also show that ABCA1 expression is reduced in the brain of A beta PP/PS1 transgenic mice. These results provide a biological function for A beta peptides and may help to define the pathogenic relationship between cholesterol metabolism in brain and AD.