PMID- 24795623
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140624
LR  - 20240104
IS  - 1663-3563 (Print)
IS  - 1663-3563 (Electronic)
IS  - 1663-3563 (Linking)
VI  - 6
DP  - 2014
TI  - The role of D-serine and glycine as co-agonists of NMDA receptors in motor neuron 
      degeneration and amyotrophic lateral sclerosis (ALS).
PG  - 10
LID - 10.3389/fnsyn.2014.00010 [doi]
LID - 10
AB  - The fundamental role of D-serine as a co-agonist at the N-methyl-D-aspartate 
      receptor (NMDAR), mediating both physiological actions of glutamate in long term 
      potentiation and nociception and also pathological effects mediated by 
      excitotoxicty, are well-established. More recently, a direct link to a chronic 
      neurodegenerative disease, amyotrophic lateral sclerosis/motor neuron disease 
      (ALS) has been suggested by findings that D-serine levels are elevated in 
      sporadic ALS and the G93A SOD1 model of ALS (Sasabe et al., 2007, 2012) and that 
      a pathogenic mutation (R199W) in the enzyme that degrades D-serine, D-amino acid 
      oxidase (DAO), co-segregates with disease in familial ALS (Mitchell et al., 
      2010). Moreover, D-serine, its biosynthetic enzyme, serine racemase (SR) and DAO 
      are abundant in human spinal cord and severely depleted in ALS. Using cell 
      culture models, we have defined the effects of R199W-DAO, and shown that it 
      activates autophagy, leads to the formation of ubiquitinated aggregates and 
      promotes apoptosis, all of which processes are attenuated by a D-serine/glycine 
      site NMDAR antagonist. These studies provide considerable insight into the 
      crosstalk between neurons and glia and also into potential therapeutic approaches 
      for ALS.
FAU - Paul, Praveen
AU  - Paul P
AD  - Neurogenetics Group, Division of Brain Sciences, Department of Medicine, Imperial 
      College London London, UK.
FAU - de Belleroche, Jackie
AU  - de Belleroche J
AD  - Neurogenetics Group, Division of Brain Sciences, Department of Medicine, Imperial 
      College London London, UK.
LA  - eng
GR  - DEBELLEROCHE/MAR10/6064/MNDA_/Motor Neurone Disease Association/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20140416
PL  - Switzerland
TA  - Front Synaptic Neurosci
JT  - Frontiers in synaptic neuroscience
JID - 101548972
PMC - PMC3997022
OTO - NOTNLM
OT  - D-amino acid oxidase (DAO)
OT  - D-serine
OT  - N-methyl-D-aspartic acid receptor (NMDAR)
OT  - amyotrophic lateral sclerosis (ALS)
OT  - apoptosis
OT  - autophagy
OT  - motor neuron disease
OT  - neurodegeneration
EDAT- 2014/05/06 06:00
MHDA- 2014/05/06 06:01
PMCR- 2014/01/01
CRDT- 2014/05/06 06:00
PHST- 2014/02/06 00:00 [received]
PHST- 2014/03/29 00:00 [accepted]
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2014/05/06 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fnsyn.2014.00010 [doi]
PST - epublish
SO  - Front Synaptic Neurosci. 2014 Apr 16;6:10. doi: 10.3389/fnsyn.2014.00010. 
      eCollection 2014.