Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction.
Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction.
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DOI：
10.4137/jen.s25516
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发表时间：
2015
影响因子：
--
通讯作者：
Keller LC
中科院分区：
文献类型：
--
作者：
Lincoln BL 2nd;Alabsi SH;Frendo N;Freund R;Keller LC
神经退行性疾病影响着全世界数百万人，随着全球人口老龄化，迫切需要提高我们对驱动神经退行性疾病的分子和细胞机制的理解。在分子水平上，神经变性涉及复杂信号通路的激活，这些信号通路驱动神经元及其细胞内成分的主动破坏。在这里，我们使用体内运动神经元损伤实验来急性诱导神经退行性变，以便跟踪黑腹果蝇损伤后发生的事件的时间顺序。我们发现，损伤部位可以根据导致轴突运输中断的神经元细胞骨架的结构缺陷快速识别。此外，神经肌肉连接处在损伤后24小时发生神经退行性事件之前积累泛素化蛋白。我们的数据提供了早期分子事件的见解，发生在轴突和神经肌肉变性在遗传上可处理的模式生物。重要的是，介导果蝇神经变性的机制在人类中是保守的。因此，这些研究对我们理解人类发生的细胞和分子事件具有重要意义，并将有助于确定未来治疗的生物医学相关靶点。
Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments.