Ca2+ Mediated Protein Citrullination Regulates Proliferation in the Regenerating and Malignant CNS

This study investigates the role of Ca²⁺-mediated protein citrullination in regulating neural stem cell proliferation in both regenerative and malignant contexts within the CNS. Using zebrafish injury models, researchers found that changes in cerebrospinal fluid (CSF) flow activate mechanoreceptors at spinal cord lesions, leading to increased Ca²⁺ activity and progenitor cell proliferation. The study identifies Ca²⁺-regulated peptidylarginine deiminase enzymes (PADs) as crucial for citrullinating intracellular targets, thereby promoting progenitor activation. Importantly, PAD inhibitors were shown to suppress the growth of aggressive medulloblastoma cells in preclinical models, suggesting potential therapeutic applications. These findings reveal a novel mechanism of proliferation control in the vertebrate CNS and underscore the importance of regenerative studies in identifying therapeutic targets.