Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovica Alasa 12-14, 11001 Belgrade, Serbia.
Curr Neuropharmacol. 2019;17(1):84-98. doi: 10.2174/1570159X15666170518151541.
Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'- nucleotidase (eN).
Studies related to the expression patterns of ectonucleotidases and their known features during brain development are reviewed, highlighting involvement of these enzymes in synapse formation and maturation in physiological as well as in pathological states.
During brain development and in adulthood all ectonucleotidases have diverse expression pattern, cell specific localization and function. NPPs are expressed at early embryonic days, but the expression of NPP3 is reduced and restricted to ependymal area in adult brain. NTPDase2 is dominant ectonucleotidase existing in the progenitor cells as well as main astrocytic NTPDase in the adult brain, while NTPDase3 is fully expressed after third postnatal week, almost exclusively on varicose fibers. Specific brain AP is functionally associated with synapse formation and this enzyme is sufficient for adenosine production during neurite growth and peak of synaptogenesis. eN is transiently associated with synapses during synaptogenesis, however in adult brain it is more glial than neuronal enzyme.
Control of extracellular adenine nucleotide levels by ectonucleotidases are important for understanding the role of purinergic signaling in developing tissues and potential targets in developmental disorders such as autism.
细胞外的腺嘌呤核苷酸和核苷，如 ATP 和腺苷，是最近发现的、研究最少的扩散信号因子之一，它们有助于胚胎期和出生后的大脑结构和功能重塑。它们在细胞外环境中的水平受到各种外核苷酸酶的严格控制：外核苷酸焦磷酸酶/磷酸二酯酶（E-NPP）、碱性磷酸酶（AP）、外核苷三磷酸二磷酸水解酶（E-NTPDases）和外 5′-核苷酸酶（eN）。
综述了与外核苷酸酶的表达模式及其在大脑发育过程中的已知特征相关的研究，强调了这些酶在生理和病理状态下参与突触形成和成熟的作用。
在大脑发育和成年期，所有外核苷酸酶都具有不同的表达模式、细胞特异性定位和功能。NPPs 在早期胚胎期表达，但 NPP3 的表达减少，局限于成年脑的室管膜区。NTPDase2 是存在于祖细胞中的主要外核苷酸酶，也是成年脑中的主要星形胶质细胞 NTPDase，而 NTPDase3 在出生后第三周后完全表达，几乎只存在于曲张纤维上。特定的脑 AP 与突触形成功能相关，这种酶在神经突生长和突触形成高峰期对腺苷的产生是足够的。eN 在突触形成过程中与突触短暂相关，但在成年脑中，它是一种比神经元酶更具胶质的酶。
外核苷酸酶对细胞外腺嘌呤核苷酸水平的控制对于理解嘌呤能信号在发育组织中的作用以及自闭症等发育障碍中的潜在靶点非常重要。
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