Antipsychotics activate the TGFβ pathway effector SMAD3.

ABSTRACT: Although effective in treating an array of neurological disorders, antipsychotics are associated with deleterious metabolic side effects. Through high-throughput screening, we previously identified phenothiazine antipsychotics as modulators of the human insulin promoter. Here, we extended our initial finding to structurally diverse typical and atypical antipsychotics. We then identified the transforming growth factor beta (TGFβ) pathway as being involved in the effect of antipsychotics on the insulin promoter, finding that antipsychotics activated SMAD3, a downstream effector of the TGFβ pathway, through a receptor distinct from the TGFβ receptor family and known neurotransmitter receptor targets of antipsychotics. Of note, antipsychotics that do not cause metabolic side effects did not ac

SUBMITTER: Cohen T 

PROVIDER: S-EPMC3991551 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature