PMID- 33218144
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20240330
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 22
DP  - 2020 Nov 18
TI  - New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and 
      Endocrine System Physiology: From Preclinical Observations to Clinical 
      Applications.
LID - 10.3390/ijms21228718 [doi]
LID - 8718
AB  - The endogenous amino acids serine and aspartate occur at high concentrations in 
      free D-form in mammalian organs, including the central nervous system and 
      endocrine glands. D-serine (D-Ser) is largely localized in the forebrain 
      structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a 
      functional role by acting as an endogenous coagonist at N-methyl-D-aspartate 
      receptors (NMDARs). Less is known about the role of free D-aspartate (D-Asp) in 
      mammals. Notably, D-Asp has a specific temporal pattern of occurrence. In fact, 
      free D-Asp is abundant during prenatal life and decreases greatly after birth in 
      concomitance with the postnatal onset of D-Asp oxidase expression, which is the 
      only enzyme known to control endogenous levels of this molecule. Conversely, in 
      the endocrine system, D-Asp concentrations enhance after birth during its 
      functional development, thereby suggesting an involvement of the amino acid in 
      the regulation of hormone biosynthesis. The substantial binding affinity for the 
      NMDAR glutamate site has led us to investigate the in vivo implications of D-Asp 
      on NMDAR-mediated responses. Herein we review the physiological function of free 
      D-Asp and of its metabolizing enzyme in regulating the functions of the brain and 
      of the neuroendocrine system based on recent genetic and pharmacological human 
      and animal studies.
FAU - Usiello, Alessandro
AU  - Usiello A
AD  - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, 
      Universita della Campania <<L. Vanvitelli>>, Via Vivaldi 43, 81100 Caserta, Italy.
AD  - CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
FAU - Di Fiore, Maria Maddalena
AU  - Di Fiore MM
AD  - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, 
      Universita della Campania <<L. Vanvitelli>>, Via Vivaldi 43, 81100 Caserta, Italy.
FAU - De Rosa, Arianna
AU  - De Rosa A
AD  - CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
AD  - Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, 
      Italy.
FAU - Falvo, Sara
AU  - Falvo S
AD  - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, 
      Universita della Campania <<L. Vanvitelli>>, Via Vivaldi 43, 81100 Caserta, Italy.
FAU - Errico, Francesco
AU  - Errico F
AD  - Dipartimento di Agraria, Universita degli Studi di Napoli Federico II, Via 
      Universita, 100, 80055 Portici, Italy.
FAU - Santillo, Alessandra
AU  - Santillo A
AD  - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, 
      Universita della Campania <<L. Vanvitelli>>, Via Vivaldi 43, 81100 Caserta, Italy.
FAU - Nuzzo, Tommaso
AU  - Nuzzo T
AD  - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, 
      Universita della Campania <<L. Vanvitelli>>, Via Vivaldi 43, 81100 Caserta, Italy.
AD  - CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
FAU - Chieffi Baccari, Gabriella
AU  - Chieffi Baccari G
AD  - Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, 
      Universita della Campania <<L. Vanvitelli>>, Via Vivaldi 43, 81100 Caserta, Italy.
LA  - eng
GR  - CUP: B68D19001880005/VALERE Project 2019/
PT  - Journal Article
PT  - Review
DEP - 20201118
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 4SR0Q8YD1X (D-Aspartic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 9002-72-6 (Growth Hormone)
RN  - EC 1.4.3.1 (D-Aspartate Oxidase)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - D-Aspartate Oxidase/metabolism
MH  - D-Aspartic Acid/*metabolism
MH  - Growth Hormone/biosynthesis
MH  - Humans
MH  - N-Methylaspartate/metabolism
MH  - Neurosecretory Systems/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Substrate Specificity
PMC - PMC7698810
OTO - NOTNLM
OT  - D-aspartate
OT  - D-aspartate oxidase
OT  - NMDA receptors
OT  - endocrine glands
OT  - hormones
COIS- The authors declare no conflict of interest.
EDAT- 2020/11/22 06:00
MHDA- 2021/03/09 06:00
PMCR- 2020/11/01
CRDT- 2020/11/21 01:01
PHST- 2020/10/14 00:00 [received]
PHST- 2020/11/11 00:00 [revised]
PHST- 2020/11/13 00:00 [accepted]
PHST- 2020/11/21 01:01 [entrez]
PHST- 2020/11/22 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/11/01 00:00 [pmc-release]
AID - ijms21228718 [pii]
AID - ijms-21-08718 [pii]
AID - 10.3390/ijms21228718 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Nov 18;21(22):8718. doi: 10.3390/ijms21228718.