Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA.
J Neurosci. 2012 Jan 11;32(2):610-5. doi: 10.1523/JNEUROSCI.3586-11.2012.
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 (Hoffman, 2010). 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 (Coleman, 2005). 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 (Xiong et al., 2010), 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.
轴突是神经元回路中易受损的组成部分，神经元配备有应对轴突损伤的机制。 Conditioning lesion（条件性损伤）就是一个研究得比较透彻的例子，先前受损的神经元有更强的能力启动新的轴突生长（Hoffman，2010）。在这里，我们研究了 Conditioning lesion（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（Coleman，2005）。我们发现，先前受过损伤的果蝇运动神经元轴突对变性的抵抗力增强。这需要保守的轴突激酶 Wallenda（Wnd）/DLK 的功能，以及下游的转录因子。由于轴突损伤导致 Wnd 的急性激活（Xiong 等人，2010），并且过表达研究表明增加 Wnd 功能足以促进对变性的保护，因此我们假设 Wnd 调节对损伤的适应性反应，使神经元能够应对轴突应激。
