Mammalian D-cysteine: A novel regulator of neural progenitor cell proliferation: Endogenous D-cysteine, the stereoisomer with rapid spontaneous in vitro racemization rate, has major neural roles

Robin Roychaudhuri, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

D-amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D-cysteine in mammalian brain. D-cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D-cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D-cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D-cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D-cysteine inhibits AKT phosphorylation at Thr 308 and Ser 473 in NPCs. D-cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D-cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D-cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD).

Original languageEnglish (US)
Article number2200002
JournalBioEssays
Volume44
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • D-amino acids
  • MARCKS (myristoylated alanine-rich C kinase substrate)
  • chirality
  • endogenous D-cysteine
  • neural progenitor cells (NPC)
  • racemization
  • serine racemase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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