Nuclear phospholipase C isoenzyme imbalance leads to pathologies in brain, hematologic, neuromuscular, and fertility disorders

Phosphoinositide-specific phospholipases C (PI-PLCs) are involved in signaling pathways related to critical cellular functions, such as cell cycle regulation, cell differentiation, and gene expression. Nuclear PI-PLCs have been studied as key enzymes, molecular targets, and clinical prognostic/diagnostic factors in many physiopathologic processes. Here, we summarize the main studies about nuclear PI-PLCs, specifically, the imbalance of isozymes such as PI-PLC1 and PI-PLC, in cerebral, hematologic, neuromuscular, and fertility disorders. PI-PLC1 and PI-PLC1 affect epilepsy, depression, and bipolar disorder. In the brain, PI-PLC1 is involved in endocannabinoid neuronal excitability and is a potentially novel signature gene for subtypes of high-grade glioma. An altered quality or quantity of PI-PLC contributes to sperm defects that result in infertility, and PI-PLC1 aberrant inositide signaling contributes to both hematologic and degenerative muscle diseases. Understanding the mechanisms behind PI-PLC involvement in human pathologies may help identify new strategies for personalized therapies of these conditions.—Ratti, S., M. Y. Follo, G. Ramazzotti, I. Faenza, R. Fiume, P-G. Suh, J. A. McCubrey, L. Manzoli, and L. Cocco. Nuclear phospholipase C isoenzyme imbalance leads to pathologies in brain, hematologic, neuromuscular, and fertility disorders.