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Role of intracellular mediators in clozapine induced ErbB1-ERK signalling in prefrontal cortical neurons: relevance to therapeutic efficacy.

Avril Pereira

Dysregulation of the epidermal growth factor (EGF) system, implicated in synaptic plasticity, long-term potentiation and dendritic spine connectivity has been linked to schizophrenia. For instance, in patient brain and blood low EGF levels resulting in compensatory up-regulation of the EGF receptor (ErbB1) is postulated to represent a hypofunctioning signalling state. Consistent with this hypothesis our preclinical in vitro and in vivo data demonstrate that the antipsychotic drug clozapine increases ErbB1 signalling via G-protein coupled receptor (GPCR) transactivation in prefrontal cortex and striatum1,2,3. The clozapine induced increase in ErbB1 signalling results in delayed activation of the extracellular signal regulated kinase (ERK) pathway with downstream activation of the transcription factors, p90RSK and c-Fos.

12th Biennial Australasian Schizophrenia Conference
13-14 May 2013 Melbourne, Australia.
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VideoRole of intracellular mediators in clozapine induced ErbB1-ERK signalling in prefrontal cortical neurons: relevance to therapeutic efficacy.Avril Pereira13'08"


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Avril Pereira

Dr Avril Pereira, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia. Centre for Neuroscience, The University of Melbourne, Australia.

Co-authors: Ye-Sol An, Suresh Sundram,
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