PMID- 29169997
OWN - NLM
STAT- MEDLINE
DCOM- 20190122
LR  - 20210214
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Print)
IS  - 0278-5846 (Linking)
VI  - 82
DP  - 2018 Mar 2
TI  - PSD95: A synaptic protein implicated in schizophrenia or autism?
PG  - 187-194
LID - S0278-5846(17)30658-9 [pii]
LID - 10.1016/j.pnpbp.2017.11.016 [doi]
AB  - The molecular components of the postsynaptic density (PSD) in excitatory synapses 
      of the brain are currently being investigated as one of the major etiologies of 
      neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic 
      density protein-95 (PSD-95) is a major regulator of synaptic maturation by 
      interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors 
      (NMDARs) and alpha-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors 
      (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming 
      evidence that associates PSD-95 disruption with cognitive and learning deficits 
      observed in SCZ and autism. For instance, recent genomic and sequencing studies 
      of psychiatric patients highlight the aberrations at the PSD of glutamatergic 
      synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency 
      shows alterations in NMDA and AMPA-receptor composition and function in specific 
      brain regions that may contribute to phenotypes observed in neuropsychiatric 
      pathologies. In this review, we describe the role of PSD-95 as an essential 
      scaffolding protein during synaptogenesis and neurodevelopment. More 
      specifically, we discuss its interactions with NMDA receptor subunits that 
      potentially affect glutamate transmission, and the formation of silent synapses 
      during critical time points of neurodevelopment. Furthermore, we describe how 
      PSD-95 may alter dendritic spine morphologies, thus regulating synaptic function 
      that influences behavioral phenotypes in SCZ versus autism. Understanding the 
      role of PSD-95 in the neuropathologies of SCZ and autism will give an insight of 
      the cellular and molecular attributes in the disorders, thus providing treatment 
      options in patients affected.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Coley, Austin A
AU  - Coley AA
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA 19129, United States.
FAU - Gao, Wen-Jun
AU  - Gao WJ
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 
      Philadelphia, PA 19129, United States. Electronic address: wg38@drexel.edu.
LA  - eng
GR  - F99 NS105185/NS/NINDS NIH HHS/United States
GR  - K00 MH124182/MH/NIMH NIH HHS/United States
GR  - R01 MH085666/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20171121
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Disks Large Homolog 4 Protein)
SB  - IM
MH  - Animals
MH  - Autism Spectrum Disorder/*metabolism
MH  - Disks Large Homolog 4 Protein/*metabolism
MH  - Humans
MH  - Schizophrenia/*metabolism
MH  - Synapses/metabolism
PMC - PMC5801047
MID - NIHMS922723
OTO - NOTNLM
OT  - AMPAR
OT  - Autism
OT  - Glutamate
OT  - NMDAR
OT  - Neurodevelopment
OT  - PSD-95
OT  - Schizophrenia
COIS- Disclosure of Conflicts of Interest The authors report no biomedical financial 
      interests or potential conflicts of interest.
EDAT- 2017/11/25 06:00
MHDA- 2019/01/23 06:00
PMCR- 2019/03/02
CRDT- 2017/11/25 06:00
PHST- 2017/08/11 00:00 [received]
PHST- 2017/10/27 00:00 [revised]
PHST- 2017/11/18 00:00 [accepted]
PHST- 2017/11/25 06:00 [pubmed]
PHST- 2019/01/23 06:00 [medline]
PHST- 2017/11/25 06:00 [entrez]
PHST- 2019/03/02 00:00 [pmc-release]
AID - S0278-5846(17)30658-9 [pii]
AID - 10.1016/j.pnpbp.2017.11.016 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:187-194. doi: 
      10.1016/j.pnpbp.2017.11.016. Epub 2017 Nov 21.