PMID- 32477178
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 11
DP  - 2020
TI  - Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and 
      Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia.
PG  - 369
LID - 10.3389/fpsyt.2020.00369 [doi]
LID - 369
AB  - Treatment-resistant schizophrenia (TRS) or suboptimal response to antipsychotics 
      affects almost 30% of schizophrenia (SCZ) patients, and it is a relevant clinical 
      issue with significant impact on the functional outcome and on the global burden 
      of disease. Among putative novel treatments, glycine-centered therapeutics (i.e. 
      sarcosine, glycine itself, D-Serine, and bitopertin) have been proposed, based on 
      a strong preclinical rationale with, however, mixed clinical results. Therefore, 
      a better appraisal of glycine interaction with the other major players of SCZ 
      pathophysiology and specifically in the framework of dopamine - glutamate 
      interactions is warranted. New methodological approaches at cutting edge of 
      technology and drug discovery have been applied to study the role of glycine in 
      glutamate signaling, both at presynaptic and post-synaptic level and have been 
      instrumental for unveiling the role of glycine in dopamine-glutamate interaction. 
      Glycine is a non-essential amino acid that plays a critical role in both 
      inhibitory and excitatory neurotransmission. In caudal areas of central nervous 
      system (CNS), such as spinal cord and brainstem, glycine acts as a powerful 
      inhibitory neurotransmitter through binding to its receptor, i.e. the Glycine 
      Receptor (GlyR). However, glycine also works as a co-agonist of the 
      N-Methyl-D-Aspartate receptor (NMDAR) in excitatory glutamatergic 
      neurotransmission. Glycine concentration in the synaptic cleft is finely tuned by 
      glycine transporters, i.e. GlyT1 and GlyT2, that regulate the neurotransmitter's 
      reuptake, with the first considered a highly potential target for psychosis 
      therapy. Reciprocal regulation of dopamine and glycine in forebrain, glycine 
      modulation of glutamate, glycine signaling interaction with postsynaptic density 
      proteins at glutamatergic synapse, and human genetics of glycinergic pathways in 
      SCZ are tackled in order to highlight the exploitation of this neurotransmitters 
      and related molecules in SCZ and TRS.
CI  - Copyright (c) 2020 de Bartolomeis, Manchia, Marmo, Vellucci, Iasevoli and Barone.
FAU - de Bartolomeis, Andrea
AU  - de Bartolomeis A
AD  - Laboratory of Molecular Psychiatry and Translational Psychiatry, Unit of 
      Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, 
      Reproductive Science and Odontostomatology, University School of Medicine of 
      Napoli Federico II, Naples, Italy.
FAU - Manchia, Mirko
AU  - Manchia M
AD  - Section of Psychiatry, Department of Medical Science and Public Health, 
      University of Cagliari, Cagliari, Italy.
AD  - Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
FAU - Marmo, Federica
AU  - Marmo F
AD  - Laboratory of Molecular Psychiatry and Translational Psychiatry, Unit of 
      Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, 
      Reproductive Science and Odontostomatology, University School of Medicine of 
      Napoli Federico II, Naples, Italy.
FAU - Vellucci, Licia
AU  - Vellucci L
AD  - Laboratory of Molecular Psychiatry and Translational Psychiatry, Unit of 
      Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, 
      Reproductive Science and Odontostomatology, University School of Medicine of 
      Napoli Federico II, Naples, Italy.
FAU - Iasevoli, Felice
AU  - Iasevoli F
AD  - Laboratory of Molecular Psychiatry and Translational Psychiatry, Unit of 
      Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, 
      Reproductive Science and Odontostomatology, University School of Medicine of 
      Napoli Federico II, Naples, Italy.
FAU - Barone, Annarita
AU  - Barone A
AD  - Laboratory of Molecular Psychiatry and Translational Psychiatry, Unit of 
      Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, 
      Reproductive Science and Odontostomatology, University School of Medicine of 
      Napoli Federico II, Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200514
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC7240307
OTO - NOTNLM
OT  - Homer
OT  - N-methyl-d-aspartate
OT  - PSD-95
OT  - antipsychotics
OT  - disk-1
OT  - dopamine
OT  - glutamate
OT  - glycine transporter 1
EDAT- 2020/06/02 06:00
MHDA- 2020/06/02 06:01
PMCR- 2020/05/14
CRDT- 2020/06/02 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/04/14 00:00 [accepted]
PHST- 2020/06/02 06:00 [entrez]
PHST- 2020/06/02 06:00 [pubmed]
PHST- 2020/06/02 06:01 [medline]
PHST- 2020/05/14 00:00 [pmc-release]
AID - 10.3389/fpsyt.2020.00369 [doi]
PST - epublish
SO  - Front Psychiatry. 2020 May 14;11:369. doi: 10.3389/fpsyt.2020.00369. eCollection 
      2020.