Mammalian D-cysteine: A novel regulator of neural progenitor cell proliferation 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
Bioessays
; 44(7): e2200002, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35484375
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).
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cysteine
/
Intracellular Signaling Peptides and Proteins
Limits:
Animals
Language:
En
Journal:
Bioessays
Journal subject:
BIOLOGIA
/
BIOLOGIA MOLECULAR
Year:
2022
Type:
Article
Affiliation country:
United States