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Targeting of Glycine Site on NMDA Receptor as a Possible New Strategy for Autism Treatment

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Abstract

The exact pathophysiology of the neurodevelopment disorder of autism is not clear and there is not any curative approach for it. There is only one FDA-approved medication for its management. Therefore, providing of novel treatments is highly required. The hypofunction of GABAergic system and glutamate toxicity are generally believed to have a causal role for autism. The antagonist of the N-methyl-d-aspartic acid (NMDA) glutamate receptor improves autism. Glycine is required for the activation of NMDA receptor. The antagonist of glycine site decreases NMDA receptor conductance. It is hypothesis that glycine site antagonists can be tested as a new strategy for the management of autism.

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References

  1. Nagy K et al (2010) Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter Type-1 inhibitor Org-24461 and Risperidone. Neurochem Res

  2. Waseem TV, Fedorovich SV (2010) Presynaptic glycine receptors influence plasma membrane potential and glutamate release. Neurochem Res 35(8):1188–1195

    Article  PubMed  CAS  Google Scholar 

  3. Socala K et al (2010) Effects of sarcosine, a glycine transporter type 1 inhibitor, in two mouse seizure models. Pharmacol Rep 62(2):392–397

    PubMed  CAS  Google Scholar 

  4. Shinohe A et al (2006) Increased serum levels of glutamate in adult patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 30(8):1472–1477

    Article  PubMed  CAS  Google Scholar 

  5. McDougle CJ et al (2005) Neurochemistry in the pathophysiology of autism. J Clin Psychiatr 66(Suppl 10):9–18

    CAS  Google Scholar 

  6. Aldred S et al (2003) Plasma amino acid levels in children with autism and their families. J Autism Dev Disord 33(1):93–97

    Article  PubMed  Google Scholar 

  7. McBain CJ et al (1989) Structural requirements for activation of the glycine coagonist site of N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Mol Pharmacol 36(4):556–565

    PubMed  CAS  Google Scholar 

  8. Kleckner NW, Dingledine R (1988) Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science 241(4867):835–837

    Article  PubMed  CAS  Google Scholar 

  9. Wood PL (2005) The NMDA receptor complex: a long and winding road to therapeutics. IDrugs 8(3):229–235

    PubMed  CAS  Google Scholar 

  10. Stanton PK et al (2009) Neuroprotection by a novel NMDAR functional glycine site partial agonist, GLYX-13. Neuroreport 20(13):1193–1197

    Article  PubMed  CAS  Google Scholar 

  11. Bergeron R et al (1998) Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci USA 95(26):15730–15734

    Article  PubMed  CAS  Google Scholar 

  12. Javitt DC (2006) Is the glycine site half saturated or half unsaturated? Effects of glutamatergic drugs in schizophrenia patients. Curr Opin Psychiatry 19(2):151–157

    Article  PubMed  Google Scholar 

  13. Pastural E et al (2009) Novel plasma phospholipid biomarkers of autism: mitochondrial dysfunction as a putative causative mechanism. Prostaglandins Leukot Essent Fatty Acids 81(4):253–264

    Article  PubMed  CAS  Google Scholar 

  14. Harada M et al (2010) Non-Invasive evaluation of the gabaergic/glutamatergic system in autistic patients observed by MEGA-editing proton MR spectroscopy using a clinical 3 tesla instrument. J Autism Dev Disord. doi:10.1007/s10803-010-1065-0

  15. Lam KS, Aman MG, Arnold LE (2006) Neurochemical correlates of autistic disorder: a review of the literature. Res Dev Disabil 27(3):254–289

    Article  PubMed  Google Scholar 

  16. Maezawa I, Jin LW (2010) Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci 30(15):5346–5356

    Article  PubMed  CAS  Google Scholar 

  17. Blaylock RL, Strunecka A (2009) Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders. Curr Med Chem 16(2):157–170

    Article  PubMed  CAS  Google Scholar 

  18. Niederhofer H (2007) Glutamate antagonists seem to be slightly effective in psychopharmacologic treatment of autism. J Clin Psychopharmacol 27(3):317–318

    Article  PubMed  Google Scholar 

  19. Erickson CA, Chambers JE (2006) Memantine for disruptive behavior in autistic disorder. J Clin Psychiatr 67(6):1000

    Article  Google Scholar 

  20. Chez MG et al (2007) Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol 22(5):574–579

    Article  PubMed  Google Scholar 

  21. Ikonomidou C, Turski L (2002) Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 1(6):383–386

    Article  PubMed  CAS  Google Scholar 

  22. Ghanizadeh A (2010) Transplantation of GABAergic cell line as a novel hypothesized treatment for autism. Epilepsy Behav 19:664

    Article  PubMed  Google Scholar 

  23. Ghanizadeh A, c-kit+ cells transplantation as a new treatment for autism, a novel hypothesis with important research and clinical implication. J Autism Dev Disord, accepted for publication

  24. Ghanizadeh A (2011) Leptin as a new approach for treatment for autism and epilepsy, a hypothesis with clinical implications. Brain Dev 33:92

    Article  PubMed  Google Scholar 

  25. Ghanizadeh A, Ghrelin as a promising therapeutic target for co-occurring autism and epilepsy. doi:10.1016/j.yebeh.2010.12.009

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Correspondence to Ahmad Ghanizadeh.

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Ghanizadeh, A. Targeting of Glycine Site on NMDA Receptor as a Possible New Strategy for Autism Treatment. Neurochem Res 36, 922–923 (2011). https://doi.org/10.1007/s11064-010-0381-2

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  • DOI: https://doi.org/10.1007/s11064-010-0381-2

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