کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2514037 1118445 2011 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: Evidence from genetically modified mouse models and pharmacological inhibition
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: Evidence from genetically modified mouse models and pharmacological inhibition
چکیده انگلیسی

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.

Inhibiting glycine transporters, GlyT1, but not GlyT2, enhances NMDA-receptor-mediated neurotransmission, thus offers an effective strategy against glutamatergic hypofunction implicated in schizophrenia, especially in the genesis of cognitive and negative symptoms.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 81, Issue 9, 1 May 2011, Pages 1065–1077
نویسندگان
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