Protease regulation: the Yin and Yang of neural development and disease.

Protease regulation: the Yin and Yang of neural development and disease.
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DOI:
10.1016/j.neuron.2011.09.012
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发表时间:
2011-10-06
期刊:
影响因子:
16.2
通讯作者:
Pfaff SL
Pfaff SL
中科院分区:
医学1区
文献类型:
--
作者:
Bai G;Pfaff SL

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神经回路的形成、维持和可塑性依赖于渐进事件和退行事件之间复杂的相互作用。在胚胎和成人神经系统内发生的动态过程中,越来越多的轴突导向分子的新功能被确定。轴突导向分子信号传导的幅度、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,我们集中在最近的进展,了解蛋白酶介导的定向轴突生长所需的指导因子的切割的作用,特别强调金属蛋白酶和γ-分泌酶的作用。由于轴突导向分子也与成人的神经变性和再生有关,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变性之间的新关系。这些发现提高了由蛋白酶控制的信号检查点可能是增强再生的有用靶点的可能性。
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.
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