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 language | English (US) |
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Article number | 2200002 |
Journal | BioEssays |
Volume | 44 |
Issue number | 7 |
DOIs | |
State | Published - 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
- General Biochemistry, Genetics and Molecular Biology