Retrograde axonal transport: pathways to cell death?

Retrograde axonal transport: pathways to cell death?
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DOI:
10.1016/j.tins.2010.03.006
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发表时间:
2010-07
影响因子:
15.9
通讯作者:
Holzbaur EL
Holzbaur EL
中科院分区:
医学1区
文献类型:
--
作者:
Perlson E;Maday S;Fu MM;Moughamian AJ;Holzbaur EL

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主动运输沿着轴突是至关重要的神经元。马达驱动的运输为远端突触提供新合成的蛋白质和脂质,并清除受损或错误折叠的蛋白质。微管马达还通过信号内体驱动长距离信号沿着轴突。虽然由神经营养因子引发的正信号已经得到了很好的研究,但最近的研究集中在轴突上的应激信号沿着。在这里,轴突运输改变和神经退行性变之间的联系进行了讨论,包括有缺陷的运输囊泡,线粒体,降解细胞器,和信号内体的肌萎缩侧索硬化症,亨廷顿,帕金森氏症和阿尔茨海默氏症的模型中的证据。运输缺陷足以诱导神经退行性变,但最近的进展表明,逆行信号通路的变化与快速进行性神经元细胞死亡相关。
Active transport along the axon is critical to the neuron. Motor-driven transport supplies the distal synapse with newly synthesized proteins and lipids, and clears damaged or misfolded proteins. Microtubule motors also drive long-distance signaling along the axon via signaling endosomes. While positive signaling initiated by neurotrophic factors has been well-studied, recent research has focused on stress signaling along the axon. Here, the connections between axonal transport alterations and neurodegeneration are discussed, including evidence for defective transport of vesicles, mitochondria, degradative organelles, and signaling endosomes in models of Amyotrophic Lateral Sclerosis, Huntington's, Parkinson's and Alzheimer's disease. Defects in transport are sufficient to induce neurodegeneration, but recent progress suggests that changes in retrograde signaling pathways correlate with rapidly progressive neuronal cell death.
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