ApoE receptor 2 controls neuronal survival in the adult brain
ApoE receptor 2 controls neuronal survival in the adult brain
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DOI：
10.1016/j.cub.2006.10.029
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发表时间：
2006-12-19
期刊：
影响因子：
9.2
通讯作者：
Herz, Joachim
中科院分区：
文献类型：
--
作者：
Beffert, Uwe;Farsian, Farnas Nematollah;Herz, Joachim
神经退行性疾病和神经创伤的中心致病特征是神经元的死亡。对诱导神经元功能障碍和死亡的因素和条件的机械理解对于设计针对创伤后或衰老期间神经元损失的有效治疗策略是必不可少的。由于载脂蛋白E（ApoE）是几种神经退行性疾病（包括阿尔茨海默病）的主要风险因素[1]，因此ApoE受体可能在疾病过程中发挥直接或间接作用。在这里，我们已经在小鼠中使用基因靶向来研究ApoE受体在神经元存活调节中的可能作用。我们证明，一个差异剪接亚型的载脂蛋白E受体，载脂蛋白E受体2（Apoer 2），是必不可少的保护神经元细胞损失在正常老化。此外，相同的剪接形式通过可能涉及Jun N-末端激酶（JNK）家族的丝氨酸/苏氨酸激酶的机制选择性地促进损伤后的神经元细胞死亡。这些发现提出了ApoE及其受体协同调节成人大脑神经元存活所必需的共同机制的可能性。
A central pathogenic feature of neurodegenerative diseases and neurotrauma is the death of neurons. A mechanistic understanding of the factors and conditions that induce the dysfunction and death of neurons is essential for devising effective treatment strategies against neuronal loss after trauma or during aging. Because Apolipoprotein E (ApoE) is a major risk factor for several neurodegenerative diseases, including Alzheimer's disease [1], a direct or indirect role of ApoE receptors in the disease process is likely. Here we have used gene targeting in mice to investigate possible roles of ApoE receptors in the regulation of neuronal survival. We demonstrate that a differentially spliced isoform of an ApoE receptor, ApoE receptor 2 (Apoer2), is essential for protection against neuronal cell loss during normal aging. Furthermore, the same splice form selectively promotes neuronal cell death after injury through mechanisms that may involve serine/threonine kinases of the Jun N-terminal kinase (JNK) family. These findings raise the possibility that ApoE and its receptors cooperatively regulate common mechanisms that are essential to neuronal survival in the adult brain.