Editor’s Pick: The Role of Purine Synthesis Pathways During Brain Development

Reviewing Editor Deanna Smith, Ph.D. selected this paper and explains why they considers it noteworthy.

This paper investigates spatial and temporal patterns of key enzymes involved in purine synthesis. The findings suggest that the two major synthetic pathways (de novo and salvage) diverge spatially and temporally in the developing brain. They show that the de novo pathway is required during embryonic development in cortical progenitors while both the de novo and salvage pathways are needed in the cerebellum. Interestingly, the salvage pathway is dominant as brains age.

Each of these pathways have unique roles at distinct stages of brain development. Inhibiting purine de novo synthesis led to the downregulation of mTOR signaling and malformations in specific embryonic brain regions, pointing to a gradient of purine demand in the developing brain. Alterations in purine metabolism are associated with both developmental and neurodegenerative diseases; these results provide new avenues for exploring this link.

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Spatiotemporal regulation of de novo and salvage purine synthesis during brain development
Tomoya Mizukoshi, Seiya Yamada, and Shin-ichi Sakakibara