Journal
AMINO ACIDS
Volume 43, Issue 5, Pages 1895-1904Publisher
SPRINGER WIEN
DOI: 10.1007/s00726-012-1370-3
Keywords
D-serine; NMDA; Glutamate; Astrocytes; Gliotransmission; Glia
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Funding
- IMHRO
- Israel Science Foundation
- ISF-Legacy Heritage Fund
- Jessie Kaplan Research Fund
- Dears Foundation
- L. Aronberg Research Fund in Neurology
- Albert Goodstein Research Fund
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [221S0003]
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The discovery of large amounts of d-serine in the brain challenged the dogma that only l-amino acids are relevant for eukaryotes. The levels of d-serine in the brain are higher than many l-amino acids and account for as much as one-third of l-serine levels. Several studies in the last decades have demonstrated a role of d-serine as an endogenous agonist of N-methyl-d-aspartate receptors (NMDARs). d-Serine is required for NMDAR activity during normal neurotransmission as well as NMDAR overactivation that takes place in neurodegenerative conditions. Still, there are many unanswered questions about d-serine neurobiology, including regulation of its synthesis, release and metabolism. Here, we review the mechanisms of d-serine synthesis by serine racemase and discuss the lessons we can learn from serine racemase knockout mice, focusing on the roles attributed to d-serine and its cellular origin.
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