Institute of Nuclear Sciences Vinča, National Institute of the Republic of Serbia
University of Belgrade
Exosomes are carriers of various bioactive molecules that enable communication between the brain and peripheral organs through the circulation. This property makes them significant new targets for diagnosis and therapy, especially in human diseases of the central nervous system, which are hard to study due to the inaccessibility of the nervous tissue. One of those diseases is multiple sclerosis, a neuroinflammatory and neurodegenerative disease for which only symptomatic therapy is available. It is also unknown whether multiple sclerosis starts in the brain or in the periphery, and what are the mechanisms leading to rapid progression in some patients, while in other patients it follows a benign course. Since exosomes are enriched with micro RNA (miRNA) molecules (small regulatory RNAs) the research in the Laboratory of Radiobiology and Molecular Genetics of the Vinča Institute is based on studying the function of miRNAs and their role in the regulation of gene expression in groups of patients with severe and mild multiple sclerosis. For this purpose, we use the integration of next generation sequencing (NGS) and bioinformatic analyzes for the characterization of identified miRNAs. Through functional studies which include the treatment of cell cultures with purified exosomes as well as the manipulation of miRNA levels by transfection of miRNA mimics and inhibitors we aim to confirm the observed potential effects of exosomal miRNAs on expression of genes involved in the ferroptosis process. The research is financed by the Science Fund of the Republic of Serbia, the Ideas program, and is carried out within the FerroReg project, coordinated by Principal research fellow Maja Živković, PhD.
The described methodology is also applied in the research of circulating exosomal miRNAs in patients with glioblastoma, another disease of the nervous system for which new approaches in effective therapy are sought. Also, exosomes from urine and carried miRNAs represent potentially new biomarkers of congenital anomalies of the kidney and urinary tract (CAKUT) and loss of renal function. Our research on exosomes in complex diseases is still at its beginning, but with the vision leading to the discovery of new diagnostic markers and potentially better therapies.
dr Maja Živković