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The new target therapy to prevent weight gain associated to atypical antipsychotics: PKCβ

Published online by Cambridge University Press:  23 March 2020

C. Pavan ,
A. Rimessi ,
B. Zavan ,
V. Vindigni  and
P. Pinton
C. Pavan
Affiliation:
University of Padova, Department of Medicine, Padova, Italy
A. Rimessi
Affiliation:
University of Ferrara, 2aDepartment of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies LTTA, Ferrara, Italy
B. Zavan
Affiliation:
University of Padova, Department of Biomedical Sciences, Padova, Italy
V. Vindigni
Affiliation:
University of Padova, Department of Neurosciences, Padova, Italy
P. Pinton
Affiliation:
University of Ferrara, 2aDepartment of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies LTTA, Ferrara, Italy

Abstract

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Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Clozapine is the most effective medication for treatment-resistant schizophrenia, in controlling aggression and suicidal behavior in psychosis. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, weight gain and metabolic side effects are well known in clinical practice exposing the patient to a greater risk of cardiovascular disorders, premature death, as well as psychosocial issues leading to non-adherence. The mechanisms underlying this pharmacologically activated disorders are still controversial. Based on our in vitro results, we have characterized in vivo the effects of the selective PKCβ inhibitor, Ruboxistaurin (LY-333531) on a preclinical model of long-term clozapine-induced weight gain. Cell biology, biochemistry and psychomotor tests have been performed on wild type and PKCβ (-/-) mutant mice to investigate the contribution of endogenous PKCβ and its pharmacological inhibitor on the neuroleptic effect of clozapine. Lastly, we also shed light on a novel aspect of the mechanism underlying of clozapine-induced weight gain, demonstrating that the clozapine-dependent PKCβ activation promote the inhibition of the lipid droplet-selective autophagy process, opening the way to new therapeutic intervention approach.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
e-Poster Walk: Psychopharmacology and pharmacoeconomics and psychoneuroimmunology
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. S370 - S371
Copyright
Copyright © European Psychiatric Association 2017
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