PDF(Pubmed)
Abstract：
Neural stem/progenitor cells (NSPCs) in specific brain regions require precisely regulated metabolite production during critical development periods. Purines-vital components of DNA, RNA, and energy carriers like ATP and GTP-are crucial metabolites in brain development. Purine levels are tightly controlled through two pathways: de novo synthesis and salvage synthesis. Enzymes driving de novo pathway are assembled into a large multienzyme complex termed the \"purinosome.\" Here, we review purine metabolism and purinosomes as spatiotemporal regulators of neural development. Notably, around postnatal day 0 (P0) during mouse cortical development, purine synthesis transitions from the de novo pathway to the salvage pathway. Inhibiting the de novo pathway affects mTORC1 pathway and leads to specific forebrain malformations. In this review, we also explore the importance of protein-protein interactions of a newly identified NSPC protein-NACHT and WD repeat domain-containing 1 (Nwd1)-in purinosome formation. Reduced Nwd1 expression disrupts purinosome formation, impacting NSPC proliferation and neuronal migration, resulting in periventricular heterotopia. Nwd1 interacts directly with phosphoribosylaminoimidazole-succinocarboxamide synthetase (PAICS), an enzyme involved in de novo purine synthesis. We anticipate this review will be valuable for researchers investigating neural development, purine metabolism, and protein-protein interactions.
摘要：
特定大脑区域中的神经干/祖细胞（NSPC）在关键发育时期需要精确调节的代谢物产生。嘌呤——DNA的重要组成部分，RNA,和能量载体，如ATP和GTP-是大脑发育的关键代谢产物。嘌呤水平通过两种途径严格控制:从头合成和补救合成。驱动从头途径的酶被组装成一个大的多酶复合物，称为“嘌呤小体”。\"这里,我们综述了嘌呤代谢和嘌呤小体作为神经发育的时空调控因子。值得注意的是,出生后第0天（P0）左右，在小鼠皮层发育过程中，嘌呤合成从从头途径过渡到补救途径。抑制从头途径会影响mTORC1途径并导致特定的前脑畸形。在这次审查中,我们还探讨了新鉴定的NSPC蛋白-NACHT和含WD重复结构域1（Nwd1）-在嘌呤小体形成中蛋白质-蛋白质相互作用的重要性。Nwd1表达降低会破坏嘌呤体的形成，影响NSPC增殖和神经元迁移，导致脑室周围异位症.Nwd1直接与磷酸核糖基氨基咪唑-琥珀羧酰胺合成酶（PAICS）相互作用，参与从头嘌呤合成的酶。我们预计这篇综述将对研究神经发育的研究人员有价值，嘌呤代谢,和蛋白质-蛋白质相互作用。
