Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients.
Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients.
复制标题
洗涤剂 - 不溶性EAAC1/EAAT3在阿尔茨海默氏病患者的海马神经元中异常积累。
DOI：
10.1111/j.1750-3639.2008.00186.x
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Cook DG
中科院分区：
文献类型：
--
作者：
Duerson K;Woltjer RL;Mookherjee P;Leverenz JB;Montine TJ;Bird TD;Pow DV;Rauen T;Cook DG
谷氨酸稳态失调可能参与阿尔茨海默病（AD）的病理过程。一旦谷氨酸从突触或其他细胞内来源释放出来，它就会被谷氨酸转运蛋白迅速清除。EAAC1（也称为EAAT3或SLC1A1）是前脑神经元中的主要谷氨酸转运蛋白。除了转运谷氨酸外，EAAC1还在调节GABA合成、减少神经元中的氧化应激方面发挥其他作用，并且在支持神经元活力方面很重要。目前，对AD中的EAAC 1知之甚少。为了解决EAAC1是否在AD中受到干扰，对来自AD和年龄和性别匹配的正常对照受试者的海马和额叶皮质的组织进行免疫组织化学。虽然EAAC1在皮质的免疫染色似乎与对照组相当，但在海马中，EAAC1异常地积聚在AD患者的CA2-CA3锥体神经元的细胞体和近端神经炎性突起中。生化分析表明，Triton X-100-不溶性EAAC 1显着增加，在AD患者的海马相比，控制和帕金森氏病患者。这些研究结果表明，异常谷氨酸转运蛋白的表达与AD相关的神经病理学和细胞内积累的洗涤剂不溶性EAAC 1是一个功能的复杂的生化病变AD，包括改变蛋白质溶解度。
Disturbed glutamate homeostasis may contribute to the pathological processes involved in Alzheimer’s disease (AD). Once glutamate is released from synapses or from other intracellular sources, it is rapidly cleared by glutamate transporters. EAAC1 (also called EAAT3 or SLC1A1) is the primary glutamate transporter in forebrain neurons. In addition to transporting glutamate, EAAC1 plays other roles in regulating GABA synthesis, reducing oxidative stress in neurons, and is important in supporting neuron viability. Currently, little is known about EAAC1 in AD. To address whether EAAC1 is disturbed in AD, immunohistochemistry was performed on tissue from hippocampus and frontal cortex of AD and normal control subjects matched for age and gender. While EAAC1 immunostaining in cortex appeared comparable to controls, in the hippocampus, EAAC1 aberrantly accumulated in the cell bodies and proximal neuritic processes of CA2–CA3 pyramidal neurons in AD patients. Biochemical analyses showed that Triton X-100-insoluble EAAC1 was significantly increased in the hippocampus of AD patients compared to both controls and Parkinson’s disease patients. These findings suggest that aberrant glutamate transporter expression is associated with AD-related neuropathology and that intracellular accumulation of detergent-insoluble EAAC1 is a feature of the complex biochemical lesions in AD that include altered protein solubility.
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影响因子：
6
作者：
Galvin, JE;Giasson, B;Trojanowski, JQ
通讯作者：
Trojanowski, JQ
影响因子：
64.8
作者：
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4.2
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25
作者：
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通讯作者：
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5.3
作者：
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通讯作者：
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