In the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia
Federica Barbagallo1, Maria Rita Assenza1, Antonino Messina2
1Department of Medicine and Surgery, Kore University of Enna, Enna, Italy
2Department of Mental Health of Enna, Psychiatry Unity, Enna Hospital, Enna, Italy
Correspondence to: Antonino Messina
Department of Mental Health of Enna, Psychiatry Unit “Umberto I” Hospital, Contrada Ferrante, Enna 94100, Italy
E-mail: a.messina@asp.enna.it
ORCID: https://orcid.org/0000-0002-3594-8542
Received: July 25, 2024; Revised: October 19, 2024; Accepted: November 14, 2024; Published online: December 3, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Intracellular cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate) and downstream cellular signal transduction are regulated by phosphodiesterases (PDEs). The neuroplasticity, neurotransmitter pathways, and neuroinflammation-controlling functions of PDEs were demonstrated in numerous in vitro and animal model studies. We comprehensively reviewed the literature regarding the expression of PDEs in various brain regions. Subsequently, articles regarding schizophrenia and PDEs were examined. The pathophysiological mechanisms of schizophrenia and PDEs in preclinical and clinical investigations are briefly reviewed. Particularly for those who do not respond to conventional antipsychotics, specific PDE inhibitors may offer innovative therapeutic alternatives. Although the connection between schizophrenia and PDEs is intriguing, additional research is required. Comprehending the brain’s PDE isoforms, their therapeutic potential, and any adverse effects of inhibiting them is essential for progress in this field.
Keywords: Neuroinflammatory diseases; Phosphodiesterase inhibitors; Adenosine cyclic monophosphate; Guanosine cyclic monophosphate; Neuronal plasticity; Schizophrenia

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