Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuron. 2011 Oct 6;72(1):9-21. doi: 10.1016/j.neuron.2011.09.012.
The formation, maintenance, and plasticity of neural circuits rely upon a complex interplay between progressive and regressive events. Increasingly, new functions are being identified for axon guidance molecules in the dynamic processes that occur within the embryonic and adult nervous system. The magnitude, duration, and spatial activity of axon guidance molecule signaling are precisely regulated by a variety of molecular mechanisms. Here we focus on recent progress in understanding the role of protease-mediated cleavage of guidance factors required for directional axon growth, with a particular emphasis on the role of metalloprotease and γ-secretase. Since axon guidance molecules have also been linked to neural degeneration and regeneration in adults, studies of guidance receptor proteolysis are beginning to define new relationships between neurodevelopment and neurodegeneration. These findings raise the possibility that the signaling checkpoints controlled by proteases could be useful targets to enhance regeneration.
神经回路的形成、维持和可塑性依赖于渐进和退行事件之间的复杂相互作用。越来越多的新功能被确定为轴突导向分子在胚胎和成人神经系统内发生的动态过程中的作用。轴突导向分子信号的幅度、持续时间和空间活性受到多种分子机制的精确调节。在这里，我们重点介绍了近年来对理解定向轴突生长所需的导向因子的蛋白酶介导切割作用的作用的理解进展，特别强调了金属蛋白酶和γ-分泌酶的作用。由于轴突导向分子也与成人的神经退行性变和再生有关，因此对导向受体蛋白水解的研究开始定义神经发育和神经退行性变之间的新关系。这些发现提出了这样一种可能性，即由蛋白酶控制的信号检查点可能是增强再生的有用目标。
