Skaper Stephen D
Department of Pharmacology and Anesthesiology, University of Padova, Padova, Italy.
Methods Mol Biol. 2012;846:13-22. doi: 10.1007/978-1-61779-536-7_2.
During development of the nervous system, neurons extend axons over considerable distances in a highly stereospecific fashion in order to innervate their targets in an appropriate manner. This involves the recognition, by the axonal growth cone, of guidance cues that determine the pathway taken by the axons. These guidance cues can act to promote and/or repel growth cone advance. The directed growth of axons is partly governed by cell adhesion molecules (CAMs) on the neuronal growth cone that bind to CAMs on the surface of other axons or nonneuronal cells. In vitro assays have established the importance of the CAMs ((neural cell adhesion molecule NCAM), N-cadherin, and L1) in promoting axonal growth over cells. Compelling evidence implicates the fibroblast growth factor receptor tyrosine kinase as the primary signal transduction molecule in the CAM pathway. CAMs are important constituents of synapses, and they appear to play important and diverse roles in regulating synaptic plasticity associated with learning and memory. Synthetic NCAM peptide mimetics corresponding to the binding site of NCAM for the fibroblast growth factor receptor promote synaptogenesis, enhance presynaptic function, and facilitate memory consolidation. Dimeric versions of functional binding motifs of N-cadherin behave as N-cadherin agonists, promoting both neuritogenesis and neuronal cell survival. Negative extracellular signals that physically direct neurite growth have also been described. The latter include the myelin inhibitory proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein. Potentiation of outgrowth-promoting signals, together with antagonism of myelin proteins or their convergent receptor, NgR, and its second messenger pathways, may provide new opportunities in the rational design of treatments for acute brain injury and neurodegenerative disorders.
在神经系统发育过程中，神经元以高度立体特异性的方式将轴突延伸相当长的距离，以便以适当的方式支配其靶标。这涉及轴突生长锥识别引导线索，这些线索决定了轴突所采取的路径。这些引导线索可起到促进和/或排斥生长锥前进的作用。轴突的定向生长部分受神经元生长锥上的细胞粘附分子（CAMs）调控，这些分子与其他轴突或非神经元细胞表面的CAMs结合。体外试验已证实CAMs（神经细胞粘附分子NCAM、N-钙粘蛋白和L1）在促进轴突在细胞上生长方面的重要性。有力证据表明成纤维细胞生长因子受体酪氨酸激酶是CAM途径中的主要信号转导分子。CAMs是突触的重要组成部分，它们似乎在调节与学习和记忆相关的突触可塑性方面发挥着重要且多样的作用。与NCAM和成纤维细胞生长因子受体结合位点相对应的合成NCAM肽模拟物可促进突触形成，增强突触前功能，并促进记忆巩固。N-钙粘蛋白功能性结合基序的二聚体形式表现为N-钙粘蛋白激动剂，可促进神经突生成和神经元细胞存活。也有描述过物理引导神经突生长的负性细胞外信号。后者包括髓磷脂抑制蛋白、Nogo、髓磷脂相关糖蛋白和少突胶质细胞-髓磷脂糖蛋白。增强促进生长的信号，同时拮抗髓磷脂蛋白或其共同受体NgR及其第二信使途径，可能为急性脑损伤和神经退行性疾病的合理治疗设计提供新的机会。
