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 Detalle_Publicacion

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

Abstract: 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-naïve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naïve patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D1-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 D1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D1 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.

 Fuente: Transl Psychiatry. 2019 Nov 18;9(1):306

Editorial: Nature Pub. Group

 Año de publicación: 2019

Nº de páginas: 12

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41398-019-0647-7

ISSN: 2158-3188

Proyecto español: SAF2016-76046-R ; SAF2013-46292-R ; SAF2017-83702-R

Url de la publicación: https://www.doi.org/10.1038/s41398-019-0647-7

Autores/as

RUSO-JULVE, FULGENCIO

POMBERO, ANA

GARCÍA-DÍAZ, NURIA

GARCIA-LOPEZ, RAQUEL

JUNCAL-RUIZ, MARÍA

GARCÍA-BLANCO, AGUSTÍN

GARRO-MARTINEZ, EMILIO

PISONERO, HELENA

ESTIRADO, ALICIA

AYESA-ARRIOLA, ROSA

LÓPEZ-GIMÉNEZ, JUAN

MAYOR JR., FEDERICO

VALDIZÁN, ELSA

MEANA, JAVIER

GONZALEZ-MAESO, JAVIER

MARTÍNEZ, SALVADOR