Ditlevsen Dorte Kornerup, Køhler Lene Boding, Berezin Vladimir, Bock Elisabeth
Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Panum Institute 6.2, Copenhagen, Denmark.
J Neurosci Res. 2007 Mar;85(4):703-11. doi: 10.1002/jnr.21175.
The neural cell adhesion molecule (NCAM) plays a crucial role in neuronal development, regeneration, and synaptic plasticity associated with learning and memory consolidation. Homophilic binding of NCAM leads to neurite extension and neuroprotection in various types of primary neurons through activation of a complex network of signalling cascades, including fibroblast growth factor receptor, Src-family kinases, the mitogen-activated protein kinase pathway, protein kinase C, phosphatidylinositol-3 kinase, and an increase in intracellular Ca(2+). Here we present data indicating an involvement of cyclic GMP in NCAM-mediated neurite outgrowth in both hippocampal and dopaminergic neurons and in NCAM-mediated neuroprotection of dopaminergic neurons. In addition, evidence is presented suggesting that NCAM mediates activation of cGMP via synthesis of nitric oxide (NO) by NO synthase (NOS) and activation of soluble guanylyl cyclase by NO, leading to an increased synthesis of cGMP and activation by cGMP of protein kinase G.
神经细胞黏附分子（NCAM）在神经元发育、再生以及与学习和记忆巩固相关的突触可塑性中起着至关重要的作用。NCAM的同源性结合通过激活包括成纤维细胞生长因子受体、Src家族激酶、丝裂原活化蛋白激酶途径、蛋白激酶C、磷脂酰肌醇-3激酶在内的复杂信号级联网络以及细胞内Ca（2+）的增加，导致多种类型的原代神经元中神经突延伸和神经保护。在这里，我们提供的数据表明环鸟苷酸（cGMP）参与了海马神经元和多巴胺能神经元中NCAM介导的神经突生长以及多巴胺能神经元的NCAM介导的神经保护。此外，有证据表明，NCAM通过一氧化氮合酶（NOS）合成一氧化氮（NO）以及NO激活可溶性鸟苷酸环化酶来介导cGMP的激活，从而导致cGMP合成增加以及蛋白激酶G被cGMP激活。
