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首页> 外文期刊>The European Journal of Neuroscience >Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity.
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Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity.

机译：APP转基因果蝇中突触标记物的轴突积累取决于NPTY基序，并与突触可塑性中的缺陷平行。

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摘要

Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular plaques, which consist mainly of beta-amyloid derived from the beta-amyloid precursor protein (APP). An additional feature of AD is axonopathy, which might contribute to impairment of cognitive functions. Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP-induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP intracellular domain. Furthermore, heterologous expression of Fe65 and JIP1b, scaffolding proteins interacting with the NPTY motif, also perturb axonal transport. Together, these data indicate that JIP1b or Fe65 may be involved in the APP-induced axonal transport defect. Moreover, we have characterized neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short-term synaptic plasticity was affected by overexpression of APP. Together, our results show that overexpression of APP induces partial stalling of axonal transport vesicles, paralleled by abnormalities in synaptic plasticity, which may provide a functional link to the deterioration of cognitive functions observed in AD.
机译：阿尔茨海默氏病（AD）的特征是神经原纤维缠结和细胞外斑块，主要由源自β-淀粉样蛋白前体蛋白（APP）的β-淀粉样蛋白组成。 AD的另一个特征是轴突病，它可能导致认知功能受损。具体而言，在AD动物模型中已经报道了轴突运输缺陷，包括过表达APP和tau的小鼠和果蝇。在这里，我们证明果蝇果蝇幼虫外周神经中APP诱导的囊泡交通堵塞取决于APP细胞内域中的四个残基NPTY主题。此外，Fe65和JIP1b的异源表达，与NPTY基序相互作用的支架蛋白，也干扰了轴突的运输。总之，这些数据表明JIP1b或Fe65可能与APP诱导的轴突运输缺陷有关。而且，我们已经表征了表达人APP的转基因幼虫在神经肌肉接头处的神经传递。与这些幼虫没有显示任何明显的运动缺陷的观察结果一致，我们发现基底突触传递没有变化。但是，短期突触可塑性受到APP过度表达的影响。在一起，我们的结果表明，APP的过度表达引起轴突运输小泡的部分停滞，与突触可塑性的异常并行，这可能提供了与AD中观察到的认知功能下降的功能联系。

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