Lim kinase, a bi-functional effector in injury-induced structural plasticity of synapses.
Lim kinase, a bi-functional effector in injury-induced structural plasticity of synapses.
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DOI：
10.4103/1673-5374.187018
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发表时间：
2016-07
影响因子：
6.1
通讯作者：
Townes-Anderson E
中科院分区：
文献类型：
--
作者：
Wang W;Townes-Anderson E
突触末梢的结构可塑性有助于神经系统的正常功能，但也有助于神经退行性变，以末梢缩回的形式，以及由于过程生长而产生的再生。突触形态变化是通过肌动蛋白细胞骨架介导的，肌动蛋白细胞骨架富集于轴突和树突末端。RhoA、Cdc42和Rac这三种rhogtpase是对细胞外刺激敏感的上游信号节点，而LIMK-cofilin活性是上调肌动蛋白周转的常见下游效应物，这对于聚合和解聚都是必要的。LIMK活性的双重作用使LIMK成为损伤诱导的突触可塑性治疗干预的潜在靶点，因为LIMK抑制可以稳定肌动蛋白细胞骨架并保持现有结构。LIMK抑制的这种治疗益处已经在损伤诱导的轴突缩回和杆状光感受器的神经鞘发芽的动物模型中得到证实。更好地了解LIMK-cofilin活性的调控及其与微管细胞骨架的相互作用，可能为促进突触再生开辟新的途径，从而有益于神经元退行性疾病。
The structural plasticity of synaptic terminals contributes to normal nervous system function but also to neural degeneration, in the form of terminal retraction, and regeneration, due to process growth. Synaptic morphological change is mediated through the actin cytoskeleton, which is enriched in axonal and dendritic terminals. Whereas the three RhoGTPases, RhoA, Cdc42 and Rac, function as upstream signaling nodes sensitive to extracellular stimuli, LIMK-cofilin activity serves as a common downstream effector to up-regulate actin turnover, which is necessary for both polymerization and depolymerization. The dual effects of LIMK activity make LIMK a potential target of therapeutic intervention for injury-induced synaptic plasticity, as LIMK inhibition can stabilize actin cytoskeleton and preserve existing structure. This therapeutic benefit of LIMK inhibition has been demonstrated in animal models of injury-induced axon retraction and neuritic sprouting by rod photoreceptors. A better understanding of the regulation of LIMK-cofilin activity and the interaction with the microtubular cytoskeleton may open new ways to promote synaptic regeneration that can benefit neuronal degenerative disease.