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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 situ in the brain and spinal cord during embryonic development that function by activating purine receptors on the surface of embryonic neural stem cells (NSCs) and mature neural progenitor cells (NPCs). Although NSCs / NPCs express m RNAs and proteins that interact with almost all nucleotide-sensitive P2X / P2Y receptors and nucleic acid-sensitive adenosine receptors, only a few of them function. ATP is sequentially degraded by heterotrimeric nucleotides into ADP, AMP and adenosine, all of which are neuro-agonists and act on different types of receptors. Nucleotides / nucleosides promote or inhibit NSC / NPC proliferation, migration and differentiation. The most common effect of all agonists, especially ATP and ADP, is to promote cell proliferation, often through P2Y1Rs and sometimes also through P2X7Rs. However, activation of P2X7R often leads to necrosis or apoptosis of NPCs. Activation of P2Y2R or blocking P2X7R can promote neural cell differentiation. At the core of the transduction mechanism is an increase in the intracellular free calcium concentration, which may be released intracellularly (G protein-coupled; P2Y) or extracellular calcium enters the cell via the activated receptor channel Internal (ATP gated ion channels; P2X). Further research will focus on elucidating how purinergic signaling regulates NSC / NPC differentiation and how the balance between resting and activated states is established through fine and dynamic regulation.