A conditioning lesion protects axons from degeneration via the Wallenda/DLK MAP kinase signaling cascade.
A conditioning lesion protects axons from degeneration via the Wallenda/DLK MAP kinase signaling cascade.
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DOI：
10.1523/jneurosci.3586-11.2012
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发表时间：
2012-01-11
期刊：
影响因子：
--
通讯作者：
Collins CA
中科院分区：
文献类型：
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作者：
Xiong X;Collins CA
轴突是神经元回路的脆弱组成部分，神经元具有对轴突损伤做出反应的机制。一个经过高度研究的例子是条件性损伤，在这种损伤中，以前受到损伤的神经元启动新轴突生长的能力增强。在这里，我们研究了条件性损伤对轴突变性的影响，轴突变性发生在损伤后的远端残端，也发生在神经病变和神经退行性疾病中。我们发现，以前受到损伤的果蝇运动神经元轴突对退化的弹性增强。这需要一个保守的轴突激酶Wallenda(WND)/DLK和下游转录因子的功能。由于轴突损伤导致WND的急性激活，而且过度表达的研究表明WND功能的增强足以促进对变性的保护，我们认为WND调节对损伤的适应性反应，使神经元能够应对轴突应激。
Axons are vulnerable components of neuronal circuitry, and neurons are equipped with mechanisms for responding to axonal injury. A highly studied example of this is the conditioning lesion, in which neurons that have been previously injured have an increased ability to initiate new axonal growth. Here we investigate the effect of a conditioning lesion on axonal degeneration, which occurs in the distal stump after injury, and also occurs in neuropathies and neurodegenerative disorders. We found that Drosophila motoneuron axons that had been previously injured had an increased resiliency to degeneration. This requires the function of a conserved axonal kinase, Wallenda (Wnd)/DLK, and a downstream transcription factor. Because axonal injury leads to acute activation of Wnd, and overexpression studies indicate that increased Wnd function is sufficient to promote protection from degeneration, we propose that Wnd regulates an adaptive response to injury that allows neurons to cope with axonal stress.