APOPROTEIN E AND NEURITE OUTGROWTH

描述：ApoE 3已被证明可以促进神经突生长， 在脂质存在下提供给神经元细胞。组织化学 有证据表明，apoE 3也在神经细胞的细胞质中积累， 细胞，并在体外与特定的微管相关 proteins. ApoE 4是apoE的一种不太普遍的亚型， apoE 3的特性这表明apoE 3在细胞内发挥作用， apoE 4不具有的正常神经元发育。这可能说明 部分原因是apoE 4是一个遗传风险因素， 阿尔茨海默病的发展。本提案的目的是 使用GT 1 -1 trk-9检测apoE 4对神经突生长的影响 暴露于外源apoE或在细胞中稳定表达apoE的细胞。 具体而言，申请人将审查是否以及通过何种机制 apoE进入细胞质，无论是特异性细胞内 靶向apoE 3也可以影响这些过程，LRP的作用 在将apoE和脂质递送到适当的细胞内隔室中。 最后，申请人将确定是否神经突生长过度，apoE 稳定性和微管稳定性是紧密相连的， apoE 3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， apoE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.