Molecular mechanisms of axon specification and neuronal disorders
Molecular mechanisms of axon specification and neuronal disorders
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DOI：
10.1196/annals.1377.013
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Kaibuchi, Kozo
中科院分区：
文献类型：
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作者：
Yoshimura, Takeshi;Arimura, Nariko;Kaibuchi, Kozo
神经元的一个基本特征是具有严重功能意义的神经元的形态极性。通常，神经元具有单个轴突和若干树突。神经元极性对于神经元胞体或树突向轴突的单向信号流是必不可少的。建立极化神经元的初始事件是单个轴突的特化。虽然研究人员正在积累轴突和树突之间的结构，分子和功能差异的目录，但我们现在才开始了解参与建立神经元极性的分子机制。我们已经描述了最近的进展，在理解细胞事件的轴突和树突的早期发展。包括我们在内的几个研究小组报道，磷脂酰肌醇3-激酶（PI 3-kinase）/Akt（也称为蛋白激酶B）/糖原合成酶激酶-3 β（GSK-3 β）/胰高血糖素反应介导蛋白-2（CRMP-2）通路对轴突特化和延伸很重要。最近的研究揭示了Rho家族小GTP酶、Par复合物和细胞因子相关蛋白在PI 3-激酶下游神经元极化的初始事件中所起的作用。我们讨论极性调节分子的作用和潜在的机制规范的轴突和树突。极性调节分子参与各种神经元疾病。本文就GSK-3 β和CRMP-2的信号转导作为治疗阿尔茨海默病（AD）和神经损伤的新靶点进行综述。这些发现可能有助于阐明AD和神经损伤的原因和治疗方法。
A cardinal feature of neurons is the morphological polarity of neurons with serious functional implications. Typically, a neuron has a single axon and several dendrites. Neuronal polarity is essential for the unidirectional signal flow from somata or dendrites to axons in neurons. The initial event in establishing a polarized neuron is the specification of a single axon. Although researchers are accumulating a catalog of structural, molecular, and functional differences between axons and dendrites, we are only now beginning to understand the molecular mechanisms involved in the establishment of neuronal polarity. We have described recent advances in the understanding of cellular events in the early development of an axon and dendrites. Several groups, including ours, reported that the phosphatidylinositol 3-kinase (PI3-kinase)/Akt (also called protein kinase B)/glycogen synthase kinase-3 beta (GSK-3 beta)/collapsin response mediator protein-2 (CRMP-2) pathway is important for axon specification and elongation. Recent studies have revealed the roles that Rho family small GTPases, the Par complex, and cytoskeleton-related proteins play in the initial events of neuronal polarization downstream of PI3-kinase. We discuss the roles of polarity-regulating molecules and the potential mechanisms underlying the specification of an axon and dendrites. Polarity-regulating molecules participate in various neuronal disorders. In this review, the signal transduction of GSK-3 beta and CRMP-2 is introduced as a new target for the treatment of Alzheimer's disease (AD) and nerve injury. These findings may help clarify causes of and treatments aimed at reversing AD and nerve injury.