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

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 p...

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Bibliographic Details
Published in:BioEssays 2022-07, Vol.44 (7), p.e2200002
Main Authors: Roychaudhuri, Robin, Snyder, Solomon H
Format: Article
Language:English
Subjects:
AKT protein
Alzheimer's disease
Amino acids
Brain
Cell division
Cell proliferation
Cells (biology)
Cysteine
FOXO1 protein
FOXO3 protein
Mammals
MARCKS protein
Mental disorders
Neonates
Neural stem cells
Neurodegenerative diseases
Neurodevelopment
Neurodevelopmental disorders
Phosphorylation
Progenitor cells
Schizophrenia
Signaling
Translocation
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Summary: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).
ISSN:0265-9247
1521-1878
DOI:10.1002/bies.202200002