INSERM UMR-S 1270, Sorbonne Université, Institut du Fer à Moulin, 75005, Paris, France.
INSERM UMR-S 1270, Sorbonne Université, Institut du Fer à Moulin, 75005, Paris, France; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular - João Lobo Antunes (iMM - JLA), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Neuropharmacology. 2023 Oct 1;237:109640. doi: 10.1016/j.neuropharm.2023.109640. Epub 2023 Jun 20.
The purinergic system includes P1 and P2 receptors, which are activated by ATP and its metabolites. They are expressed in adult neuronal and glial cells and are crucial in brain function, including neuromodulation and neuronal signaling. As P1 and P2 receptors are expressed throughout embryogenesis and development, purinergic signaling also has an important role in the development of the peripheral and central nervous system. In this review, we present the expression pattern and activity of purinergic receptors and of their signaling pathways during embryonic and postnatal development of the nervous system. In particular, we review the involvement of the purinergic signaling in all the crucial steps of brain development i.e. in neural stem cell proliferation, neuronal differentiation and migration as well as in astrogliogenesis and oligodendrogenesis. Then, we review data showing a crucial role of the ATP and adenosine signaling pathways in the formation of the peripheral neuromuscular junction and of central GABAergic and glutamatergic synapses. Finally, we examine the consequences of deregulation of the purinergic system during development and discuss the therapeutic potential of targeting it at adult stage in diseases with reactivation of the ATP and adenosine pathway. This article is part of the Special Issue on "Purinergic Signaling: 50 years".
嘌呤能系统包括 P1 和 P2 受体，它们被 ATP 及其代谢物激活。它们在成年神经元和神经胶质细胞中表达，并在脑功能中起关键作用，包括神经调节和神经元信号传递。由于 P1 和 P2 受体在胚胎发生和发育过程中表达，嘌呤能信号传递在周围和中枢神经系统的发育中也具有重要作用。在这篇综述中，我们介绍了嘌呤能受体及其信号通路在神经系统胚胎发生和出生后发育过程中的表达模式和活性。特别是，我们综述了嘌呤能信号传递在脑发育的所有关键步骤中的参与，即在神经干细胞增殖、神经元分化和迁移以及星形胶质细胞发生和少突胶质细胞发生中。然后，我们回顾了数据表明 ATP 和腺苷信号通路在形成周围神经肌肉接头以及中央 GABA 能和谷氨酸能突触中的关键作用。最后，我们研究了嘌呤能系统在发育过程中失调的后果，并讨论了在 ATP 和腺苷途径重新激活的疾病中靶向它在成年阶段的治疗潜力。本文是“嘌呤能信号传递：50 年”特刊的一部分。
