Finding a druggable target for schizophrenia

Rico, Beatriz

doi:10.1073/pnas.1209389109

Cited by 12 publications

(8 citation statements)

References 22 publications

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“…However, as indicated above, Law et al [11] demonstrated that HALO reduces PIK3CD mRNA expression only to 80% of the control. The degree of reduction in the gene expression does not preclude any clinical relevance of the effect, particularly as the extent of desirable decrease was not established [28] .…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

Karbownik¹,

Szemraj²,

Wieteska³

et al. 2016

Pharmacology

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Background/Aims: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. Methods: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. Results: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. Conclusions: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

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Section: Discussionmentioning

confidence: 99%

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

Karbownik¹,

Szemraj²,

Wieteska³

et al. 2016

Pharmacology

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“…In spite of this, disorders continue to be stereotypically depicted as homogeneous. A case in point is the diagnosis of schizophrenia, which in prestigious scientific journals typically is described homogeneously in line with its early twentieth century asylum origins as a 'devastating brain disease' or similar stereotype (Sawa & Snyder, 2002;Corfas et al 2004;Walsh et al 2008;Esslinger et al 2009;McDannald et al 2011;Rico, 2012). Patients receiving the diagnosis of schizophrenia are thus exposed to pressure to conform to an identity that is compatible with this stereotype, resulting in a strong desire to 'recover' from this experience.…”

Section: The Principle Of Contextual Precision Diagnosismentioning

confidence: 99%

Psychiatry beyond labels: introducingcontextual precision diagnosisacross stages of psychopathology

Delespaul

Wigman

et al. 2013

Psychol. Med.

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“…Thus, in human brains and in lymphoblastoid B-cell lines (LCLs) of subjects with schizophrenia, an ErbB4 risk haplotype (AGG; rs7598440, rs839523, rs707284) was found to be associated with elevated ErbB4 CYT-1 transcription and consequently raised expression of PIK3CD (p110δ). Importantly, despite augmented PIK3CD levels, PI3K signaling is reduced; this surprising result points to a complex deregulation of the NRG1/ERBB4/PI3K pathway, with a negative effect on the PI3K signaling in this disease [8,134]. Law and colleagues cite similar results regarding elevated levels of PIK3CD, accompanied by dampened PI3K signaling in neuroblastoma tumors [135,136], an effect suggesting that PIK3CD may act as a tumor suppressor.…”

Section: Pi3kmentioning

confidence: 85%

The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia

Enriquez-barreto¹,

Morales²

2016

MCT

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This review is focused in PI3K’s involvement in two widespread mental disorders: Autism and Schizophrenia. A largebody of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases ofbrain synaptic circuit’s development or later modulating synaptic function and plasticity. Autism related disordersand Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult,although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the roleof the PI3K signaling pathway. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity;thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recentevidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia,together with the plausible new pharmacological paths targeting this signaling pathway.

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Finding a druggable target for schizophrenia

Cited by 12 publications

References 22 publications

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

Psychiatry beyond labels: introducingcontextual precision diagnosisacross stages of psychopathology

The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia

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