CELLULAR PROCESSING OF APOE3 AND APOE4

最近的遗传学证据表明，阿尔茨海默氏症的发病年龄 疾病(AD)与血液中 载脂蛋白E(ApoE)变异体4.单一氨基酸如何从 变异体3和变异体4会导致神经变性，而唐格斯不会 明白了。载脂蛋白E有两条明显的作用途径可能导致 神经退行性变；或者，apoE4可能进入细胞质 通过内吞途径中的跨膜翻转过程，或者它可以 正在诱导一个导致退化过程的信号。我们建议 探讨背根神经节摄取apoE3和E4的途径 神经元及其刺激分化的反应 在可能的机制之间。我们对神经元的长期兴趣 运输和加工促使我们解决 载脂蛋白E3和E4的生物学差异及其可能的影响 这两种形式之间的神经元和生化差异 我们将确定这些差异是否以及如何导致 细胞运动性的改变。使用专门标记的apoE和/或 特定的抗体，我们将跟踪载脂蛋白E和刺激的命运 它们所引出的。我们将描述轴突延伸和 并将分析其对微管的影响。 从属运动性。这些研究将确定细胞途径 APOE加工及其对运动能力影响的基础。

Recent genetic evidence has shown that the age of onset of Alzheimer's disease (AD) correlates inversely with the concentration of the apolipoprotein E (apoE) variant 4. How the single amino acid change from variant 3 to variant 4 leads to neurodegeneration and tangles is not understood. There are two obvious routes of action of apoE that could lead to neurodegeneration; either, apoE4 could be entering the cell cytoplasm through a transmembrane flip process in the endocytic pathway or it could be inducing a signal that results in the degenerative process. We propose to follow the paths of uptake of apoE3 and E4 in dorsal root ganglion (DRG) neurons as well as the responses that they stimulate to differentiate between the possible mechanisms. Our long-term interest in neuronal transport and processing has stimulated us to address the question of the biological differences between apoE3 and E4 and how they might affect neuronal and biochemical differences between the two forms have been observed and we will determine if and how those differences can result in changes in cellular motility. Using specifically tagged apoEs and/or specific antibodies, we will follow the fate of the apoEs and the stimuli that they elicit. We will characterize the changes in axon extension and branching caused by apoE4 and will analyze its effect on microtubule- dependent motility. These studies will identify the cellular pathway of apoE processing and the bases of its effects on motility.