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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death.
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Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death.

机译：胶原蛋白应答介导蛋白4a（CRMP4a）在突变SOD1小鼠的运动神经元中被上调，并且可以触发运动神经元轴突变性和细胞死亡。

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摘要

Embryonic motoneurons from mutant SOD1 (mSOD1) mouse models of amyotrophic lateral sclerosis (ALS), but not wild-type motoneurons, can be triggered to die by exposure to nitric oxide (NO), leading to activation of a motoneuron-specific signaling pathway downstream of the death receptor Fas/CD95. To identify effectors of mSOD1-dependent cell death, we performed a proteomic analysis. Treatment of cultured mSOD1 motoneurons with NO led to a 2.5-fold increase in levels of collapsin response mediator protein 4a (CRMP4a). In vivo, the percentage of mSOD1 lumbar motoneurons expressing CRMP4 in mSOD1 mice increased progressively from presymptomatic to early-onset stages, reaching a maximum of 25%. Forced adeno-associated virus (AAV)-mediated expression of CRMP4a in wild-type motoneurons in vitro triggered a process of axonal degeneration and cell death affecting 60% of motoneurons, whereas silencing of CRMP4a in mSOD1 motoneurons protected them from NO-induced death. In vivo, AAV-mediated overexpression of CRMP4a but not CRMP2 led to the death of 30% of the lumbar motoneurons and an 18% increase in denervation of neuromuscular junctions in the gastrocnemius muscle. Our data identify CRMP4a as a potential early effector in the neurodegenerative process in ALS.
机译：来自肌萎缩性侧索硬化症（ALS）突变型SOD1（mSOD1）小鼠模型的胚胎运动神经元，但不是野生型运动神经元，可以通过暴露于一氧化氮（NO）触发死亡，从而导致下游的运动神经元特异性信号通路被激活死亡受体Fas / CD95的表达。为了鉴定mSOD1依赖性细胞死亡的效应子，我们进行了蛋白质组学分析。用NO处理培养的mSOD1运动神经元导致胶原蛋白反应介导蛋白4a（CRMP4a）的水平增加了2.5倍。在体内，mSOD1小鼠中表达CRMP4的mSOD1腰运动神经元的百分比从症状发作前到发病初期逐渐增加，最高达到25％。强迫腺相关病毒（AAV）介导的野生型运动神经元中CRMP4a的表达在体外触发了轴突变性和细胞死亡的过程，影响了60％的运动神经元，而在mSOD1运动神经元中CRMP4a的沉默保护了它们免受NO诱导的死亡。在体内，AAV介导的CRMP4a过表达而不是CRMP2导致30％的腰部运动神经元死亡，腓肠肌神经肌肉接头失神经增加18％。我们的数据确定CRMP4a是ALS神经变性过程中的潜在早期效应物。

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