Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics

A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood m...

Descripción completa

Detalles Bibliográficos
Autores: Ruso-Julve, F, Pombero, A, Pilar-Cuellar, F, Garcia-Diaz, N, Garcia-Lopez, R, Juncal-Ruiz, M, Castro, E, Diaz, A, Vazquez-Bourgon, J, Garcia-Blanco, A, Garro-Martinez, E, Pisonero, H, Estirado, A, Ayesa-Arriola, R, Lopez-Gimenez, J, Mayor, F, Valdizan, E, Meana, J, Gonzalez-Maeso, J, Martinez, S, Vaque, JP, Crespo-Facorro, B
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p4092
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/4092
Access Level:acceso abierto
id ES_8b7748e9ad0196e4d5d8ca14b91c655a
oai_identifier_str oai:incliva.fundanetsuite.com:p4092
network_acronym_str ES
network_name_str España
repository_id_str
spelling Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychoticsRuso-Julve, FPombero, APilar-Cuellar, FGarcia-Diaz, NGarcia-Lopez, RJuncal-Ruiz, MCastro, EDiaz, AVazquez-Bourgon, JGarcia-Blanco, AGarro-Martinez, EPisonero, HEstirado, AAyesa-Arriola, RLopez-Gimenez, JMayor, FValdizan, EMeana, JGonzalez-Maeso, JMartinez, SVaque, JPCrespo-Facorro, BA better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-na)Ve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naive patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D-1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D-1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D-1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.SPRINGERNATURE2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/4092Translational PsychiatryISSN: 21583188reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p40922026-06-07T16:35:31Z
dc.title.none.fl_str_mv Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
title Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
spellingShingle Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
Ruso-Julve, F
title_short Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
title_full Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
title_fullStr Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
title_full_unstemmed Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
title_sort Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
dc.creator.none.fl_str_mv Ruso-Julve, F
Pombero, A
Pilar-Cuellar, F
Garcia-Diaz, N
Garcia-Lopez, R
Juncal-Ruiz, M
Castro, E
Diaz, A
Vazquez-Bourgon, J
Garcia-Blanco, A
Garro-Martinez, E
Pisonero, H
Estirado, A
Ayesa-Arriola, R
Lopez-Gimenez, J
Mayor, F
Valdizan, E
Meana, J
Gonzalez-Maeso, J
Martinez, S
Vaque, JP
Crespo-Facorro, B
author Ruso-Julve, F
author_facet Ruso-Julve, F
Pombero, A
Pilar-Cuellar, F
Garcia-Diaz, N
Garcia-Lopez, R
Juncal-Ruiz, M
Castro, E
Diaz, A
Vazquez-Bourgon, J
Garcia-Blanco, A
Garro-Martinez, E
Pisonero, H
Estirado, A
Ayesa-Arriola, R
Lopez-Gimenez, J
Mayor, F
Valdizan, E
Meana, J
Gonzalez-Maeso, J
Martinez, S
Vaque, JP
Crespo-Facorro, B
author_role author
author2 Pombero, A
Pilar-Cuellar, F
Garcia-Diaz, N
Garcia-Lopez, R
Juncal-Ruiz, M
Castro, E
Diaz, A
Vazquez-Bourgon, J
Garcia-Blanco, A
Garro-Martinez, E
Pisonero, H
Estirado, A
Ayesa-Arriola, R
Lopez-Gimenez, J
Mayor, F
Valdizan, E
Meana, J
Gonzalez-Maeso, J
Martinez, S
Vaque, JP
Crespo-Facorro, B
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
description A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-na)Ve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naive patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D-1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D-1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D-1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/4092
url https://incliva.portalinvestigacion.com/publicaciones/4092
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGERNATURE
publisher.none.fl_str_mv SPRINGERNATURE
dc.source.none.fl_str_mv Translational Psychiatry
ISSN: 21583188
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412811308793856
score 15.812429

Similares en LA Referencia