Abstract
Despite the recent therapeutic advances in neurological disorders, curative therapy remains a serious challenge in many cases. Even though recent years have witnessed the development of gene therapy from among the different therapeutic approaches affecting pathophysiological mechanisms, intriguing aspects exist regarding the effectiveness, safety, and mechanism of action of gene therapies. Micro ribonucleic acid (microRNA-miRNA), as a fundamental gene regulator, regulates messenger ribonucleic acid (mRNA) by directly binding through the 3'-untranslated region (3'-UTR). MicroRNA-219 is a specific brain-enriched miRNA associated with neurodevelopmental disorders that play crucial roles in the differentiation of oligodendrocyte progenitorcells, promotion of oligodendrocyte maturation, remyelination, and cognitive functions to the extent that it can be considered a potential therapeutic option for demyelination in multiple sclerosis and spinal cord injury and reverse chronic inflammation pains. Additionally, miR-219 regulates the circadian clock, influencing the duration of the circadian clock period. This regulation can impact mood stability and is associated with phase fluctuations in bipolar patients. Furthermore, miR-219 also plays a role in modulating tau toxicity, which is relevant to the pathophysiology of Alzheimer's disease and schizophrenia. Finally, it reportedly has protective effects against seizures and Parkinson's disease, as well as neoplasms, by inhibiting proliferation, suppressing invasion, and inducing cell death in tumor cells. Exploring the miR-219 molecular pathways and their therapeutic effects on central nervous system disorders and the mechanisms involved, the present review study aims to illustrate how this information may change the future of gene therapy.