APOPROTEIN E AND NEURITE OUTGROWTH

描述：APOE3已被证明在以下情况下促进轴突生长 在脂质存在的情况下提供给神经细胞。组织化学 有证据表明apoE3也聚集在神经元的细胞质中。 细胞和它在体外与特定的微管相关 蛋白质。载脂蛋白E4是载脂蛋白E的一种不太常见的异构体，但不具有这些特征 ApoE3的性质。这表明apoE3在细胞内具有作用。 与apoE4不同的正常神经元发育。这可能说明了 部分原因是载脂蛋白E4是一种遗传风险因素 阿尔茨海默病的发展。这项提议的目标是 用GT1-1trk-9检测apoE4对神经突起生长的影响 暴露于外源载脂蛋白E或稳定表达载脂蛋白E的细胞。 具体地说，申请人将审查是否以及通过什么机制 APOE获得进入细胞质的途径，无论是特定于细胞内的 靶向apoE3也可以影响这些过程，以及LRP的作用 将载脂蛋白E和脂类运送到适当的细胞内隔室。 最后，申请者将确定轴突是否超过了apoE 稳定性和微管稳定性是紧密耦合的 ApoE3的相同结构域是否影响这三个过程。这些 结果应该提供有关生理作用的重要信息。 载脂蛋白E在神经元生长和分化中的作用。

DESCRIPTION: ApoE3 has been shown to promote neurite outgrowth when provided to neuronal cells in the presence of lipid. Histochemical evidence suggests that apoE3 also accumulates in the cytoplasm of neuronal cells and it associates in vitro with specific microtubule associated proteins. ApoE4, a less prevalent isoform of apoE, does not share these properties of apoE3. This suggests that apoE3 has a intracellular role in normal neuronal development that is not shared by apoE4. This may account in part for the fact that apoE4 is a genetic risk factor for the development of Alzheimer's disease. The goal of this proposal is to examine the influence of apoE4 on neurite outgrowth using GT1-1 trk-9 cells exposed to exogenous apoE or stably expressing apoE in the cells. Specifically, the applicant will examine whether and by what mechanism apoE gains access to the cytoplasm, whether specific intracellular targeting of apoE3 can also influence these processes, and the role of LRP in delivering apoE and lipid to the appropriate intracellular compartment. Finally the applicant will determine whether neurite outgrown, apoE stability, and microtubule stability are tightly coupled by determining whether the same domains of apoE3 influence these three processes. These results should provide important information about the physiological role of apoE in neuronal growth and differentiation.