嘌呤信号通路对成熟神经祖细胞功能的调节

Regulation of adult neural progenitor cell functions by purinergic signaling

细胞外的嘌呤是胚胎发育过程中脑和脊髓原位内的信号分子,它们通过激活胚胎神经干细胞(NSCs)及成熟神经祖细胞(NPCs)表面的嘌呤受体发挥作用。虽然NSCs/NPCs内表达了能和几乎所有核苷酸敏感型P2X/P2Y受体和核酸敏感型腺苷受体相作用的m RNA和蛋白,但其中只有一部分具有功能。ATP被异位核苷酸酶依次降解为ADP,AMP和腺苷,它们都是神经激动剂并作用于不同类型的受体。核苷酸/核苷促进或抑制NSC/NPC增殖、迁移和分化。所有激动剂(特别是ATP和ADP)的最普遍的作用是促进细胞增殖,常通过P2Y1Rs,有时也通过P2X7Rs。但P2X7R的激活通常导致NPCs的坏死或凋亡。激活P2Y2R或阻断P2X7R可促进神经细胞的分化。转导机制的核心是细胞内游离钙离子浓度的升高,游离的钙离子可能来自细胞内的释放(G蛋白偶联;P2Y),或细胞外的钙离子通过被激活的受体通道进入细胞内(ATP门控离子通道;P2X)。进一步的研究将着重阐明嘌呤信号通道如何调控NSC/NPC的分化,以及静息和活化状态之间的平衡如何通过精细和动态的调节来建立。

Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells （NSCs） and adult neural progenitor cells （NPCs）. Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, mi- gration and differentiation. The most ubiquitous effect of all agonists （especially of ATP and ADP） appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transductionmechanism of either receptor is the increase of the intracellu- lar free Ca2 ＋ concentration, which may arise due to its release from intracellular storage sites （G protein-coupling; P2Y） or due to its passage through the receptor-channel itself from the extracellular space （ATP-gated ion channel; P2X）. Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65： 213-230.