Barbagallo Federica, Assenza Maria Rita, Messina Antonino
Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
Department of Mental Health of Enna, Psychiatry Unity, Enna Hospital, Enna, Italy.
Clin Psychopharmacol Neurosci. 2025 Feb 28;23(1):15-31. doi: 10.9758/cpn.24.1229. Epub 2024 Dec 3.
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.
细胞内环核苷酸(环磷酸腺苷和环磷酸鸟苷)及下游细胞信号转导由磷酸二酯酶(PDEs)调控。众多体外和动物模型研究证实了PDEs在神经可塑性、神经递质通路及神经炎症控制功能方面的作用。我们全面回顾了有关PDEs在不同脑区表达的文献。随后,查阅了有关精神分裂症和PDEs的文章。简要综述了精神分裂症和PDEs在临床前和临床研究中的病理生理机制。特别是对于那些对传统抗精神病药物无反应的患者,特定的PDE抑制剂可能提供创新的治疗选择。尽管精神分裂症与PDEs之间的联系很有趣,但仍需进一步研究。了解大脑中的PDE同工型、它们的治疗潜力以及抑制它们的任何不良反应对于该领域的进展至关重要。