Higashida Haruhiro, Salmina Alla B, Olovyannikova Raissa Ya, Hashii Minako, Yokoyama Shigeru, Koizumi Keita, Jin Duo, Liu Hong-Xiang, Lopatina Olga, Amina Sarwat, Islam Mohammad Saharul, Huang Jian-Jun, Noda Mami
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Neurochem Int. 2007 Jul-Sep;51(2-4):192-9. doi: 10.1016/j.neuint.2007.06.023. Epub 2007 Jun 28.
beta-NAD(+) is as abundant as ATP in neuronal cells. beta-NAD(+) functions not only as a coenzyme but also as a substrate. beta-NAD(+)-utilizing enzymes are involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a universal Ca(2+) mobilizer from intracellular stores, from beta-NAD(+). cADPR acts through activation/modulation of ryanodine receptor Ca(2+) releasing Ca(2+) channels. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Moreover, cADPR/CD38 is critical in oxytocin release from the hypothalamic cell dendrites and nerve terminals in the posterior pituitary. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or synthetic cADPR analogues may provide new therapeutic opportunities for treatment of neurodevelopmental disorders.
β-NAD(+)在神经元细胞中的含量与ATP一样丰富。β-NAD(+)不仅作为辅酶发挥作用，还作为底物。利用β-NAD(+)的酶参与信号转导。我们关注的是ADP-核糖基环化酶/CD38，它能从β-NAD(+)合成环ADP-核糖（cADPR），一种从细胞内储存中释放Ca(2+)的通用Ca(2+)动员剂。cADPR通过激活/调节ryanodine受体Ca(2+)释放Ca(2+)通道发挥作用。神经元细胞中cADPR的合成通过不同途径和各种因素受到刺激或调节。各种神经递质受体与ADP-核糖基环化酶的亚型特异性偶联证实了该酶参与神经元和神经胶质细胞的信号转导。此外，cADPR/CD38对下丘脑细胞树突和垂体后叶神经末梢释放催产素至关重要。因此，通过ADP-核糖基环化酶活性或合成cADPR类似物对细胞内cADPR水平进行药理学调控可能为神经发育障碍的治疗提供新的治疗机会。
