Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: Evidence from genetically modified mouse models and pharmacological inhibition

Hanns Möhler, Detlev Boison, Philipp Singer, Joram Feldon, Meike Pauly-Evers, Kay Yan Benjamin Yee

Research output: Journal article publicationReview articleAcademic researchpeer-review

40 Citations (Scopus)

Abstract

Schizophrenia is characterized by positive symptoms such as hallucinations, negative symptoms such as blunted affect, and symptoms of cognitive deficiency such as deficits in working memory and selective attention. N-methyl-d-aspartate receptor (NMDAR) hypofunction has been implicated in all three pathophysiological aspects of the disease. Due to the severe side effects of direct NMDAR agonists, targeting the modulatory co-agonist glycine-B site of the NMDAR is considered to be a promising strategy to ameliorate NMDAR hypofunction. To assess the antipsychotic and pro-cognitive potential of this approach, we examine the strategies designed to enhance glycine-B site occupancy through glycine transporter 1 (GlyT1) blockade. Among the existing transgenic mouse models with GlyT1 deficits, the one specifically targeting forebrain neuronal GlyT1 has yielded the most promising data on cognitive enhancement. Parallel advances in the pharmacology of GlyT1 inhibition point not only to an enhancement of attention, learning and memory but also include suggestions of mood enhancing effects that might be valuable for treating negative symptoms. Thus, interventions at GlyT1 are highly effective in modifying multiple brain functions, and dissection of their respective mechanisms is expected to further maximize their therapeutic potential for human mental diseases.
Original languageEnglish
Pages (from-to)1065-1077
Number of pages13
JournalBiochemical Pharmacology
Volume81
Issue number9
DOIs
Publication statusPublished - 1 May 2011
Externally publishedYes

Keywords

  • Antipsychotic
  • Attention
  • Cognition
  • Learning
  • NMDA

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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