D-cysteine is an endogenous regulator of neural progenitor cell dynamics in the mammalian brain.
Evan R. Semenza,Maged M. Harraz,Efrat Abramson,Adarsha P. Malla,Chirag Vasavda,Moataz M. Gadalla,Michael D. Kornberg,Solomon H. Snyder,Robin Roychaudhuri +8 more
TLDR
Using chiral high-performance liquid chromatography and a stereospecific luciferase assay, this paper identified endogenous d-cysteine in the mammalian brain and implicate it as a physiologic regulator of NPC homeostasis in the developing brain.Abstract:
d-amino acids are increasingly recognized as important signaling molecules in the mammalian central nervous system. However, the d-stereoisomer of the amino acid with the fastest spontaneous racemization ratein vitro in vitro, cysteine, has not been examined in mammals. Using chiral high-performance liquid chromatography and a stereospecific luciferase assay, we identify endogenous d-cysteine in the mammalian brain. We identify serine racemase (SR), which generates the N-methyl-d-aspartate (NMDA) glutamate receptor coagonist d-serine, as a candidate biosynthetic enzyme for d-cysteine. d-cysteine is enriched more than 20-fold in the embryonic mouse brain compared with the adult brain. d-cysteine reduces the proliferation of cultured mouse embryonic neural progenitor cells (NPCs) by ∼50%, effects not shared with d-serine or l-cysteine. The antiproliferative effect of d-cysteine is mediated by the transcription factors FoxO1 and FoxO3a. The selective influence of d-cysteine on NPC proliferation is reflected in overgrowth and aberrant lamination of the cerebral cortex in neonatal SR knockout mice. Finally, we perform an unbiased screen for d-cysteine-binding proteins in NPCs by immunoprecipitation with a d-cysteine-specific antibody followed by mass spectrometry. This approach identifies myristoylated alanine-rich C-kinase substrate (MARCKS) as a putative d-cysteine-binding protein. Together, these results establish endogenous mammalian d-cysteine and implicate it as a physiologic regulator of NPC homeostasis in the developing brain.read more
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Mammalian D‐cysteine: A novel regulator of neural progenitor cell proliferation
TL;DR: It is hypothesized 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.
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D-Amino Acids as a Biomarker in Schizophrenia
TL;DR: An outline of the roles of D-amino acids in brain health and neuropsychiatric disorders with a focus on schizophrenia is provided, which may shed light on some of the superior diagnoses and/or treatments of schizophrenia.
Journal ArticleDOI
Promising Application of D-Amino Acids toward Clinical Therapy
TL;DR: In this article , the potential of D-amino acids as therapeutic agents for treating neurological disease or tissue/organ injury, ameliorating reproduction function, preventing biofilm infection, and inhibiting cancer cell growth.
Journal ArticleDOI
A Novel Stereospecific Bioluminescent Assay for Detection of Endogenous d-Cysteine.
TL;DR: In this paper , a stereospecific, bioluminescent assay was used to identify endogenous d-cysteine in substantial amounts in the eye, brain, and pancreas of mice.
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D-Cysteine Ethyl Ester Reverses the Deleterious Effects of Morphine on Breathing and Arterial Blood–Gas Chemistry in Freely-Moving Rats
Paulina M. Getsy,Santhosh M. Baby,Walter J. May,Alex P. Young,Benjamin Gaston,Matthew R. Hodges,Hubert V. Forster,James N. Bates,Christopher G. Wilson,Tristan H. Lewis,Yee-Hee Hsieh,Stephen J. Lewis +11 more
TL;DR: D-CYSee and related thiol esters may have clinical potential for the reversal of the adverse effects of opioids on breathing and gas exchange, while largely sparing antinociception and sedation.
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