Neuroinflammatory role of miRNA in multiple sclerosis

MikroRNA (miRNA) male su nekodirajuće molekule koje sudjeluju u post-transkripcijskoj regulaciji genske ekspresije. Vezanjem za komplementarne sekvence unutar ciljne glasničke RNA (mRNA) molekule uzrokuju degradaciju mRNA ili inhibiciju translacije. Regulacijom genske ekspresije utječu na ključne stanične procese poput diferencijacije, proliferacije i apoptoze. Deregulacija ekspresije miRNA povezana je s razvojem neuroinflamacije kod mnogih neurodegenerativnih bolesti, uključujući multiplu sklerozu. Multipla skleroza autoimuni je poremećaj karakteriziran gubitkom imunološke tolerancije prema mijelinskim antigenima i stvaranjem autoreaktivnih T limfocita. Smatra se da bolest uzrokuje kombinacija okolišnih čimbenika i rizičnih gena. Kod multiple skleroze dolazi do autoimunog odgovora autoreaktivnih T limfocita na mijelinske antigene, što uzrokuje lučenje pro-inflamatornih citokina i aktivaciju stanica imunološkog sustava te vodi do neuroinflamacije, demijelinizacije i degeneracije aksona. Rastući broj istraživanja potvrđuje ulogu miRNA molekula u regulaciji neuroinflamacije. miRNA mogu imati pro-inflamatorni ili anti-inflamatorni učinak i sukladno s time regulacijom njihove ekspresije može doći do pozitivnog ili negativnog djelovanja na razvoj neuroinflamacije. Daljnjim istraživanjem mehanizama regulacije miRNA dobit će se dublji uvid u patogenezu multiple skleroze, kako bi se identificirale miRNA pogodne za ulogu terapeutskih meta.microRNA (miRNA) are small non-coding molecules that take part in post-transcriptional regulation of gene expression. They bind to the complementary sequences within the target messenger RNA (mRNA) molecule and cause mRNA degradation or inhibition of translation. By regulating the gene expression they affect key cellular processes, such as differentiation, proliferation and apoptosis. Dysregulation of miRNA expression is associated with the development of neuroinflammation in different neurodegenerative disorders, including multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by the loss of immune tolerance to myelin antigens and generation of autoreactive T lymphocytes. It is thought that the cause of the disease is a combination of environmental factors and risk genes. In multiple sclerosis, autoimmune response is induced by T lymphocytes reacting to myelin antigens, which causes pro-inflammatory cytokine secretion and activation of immune cells which eventually leads to neuroinflammation, demyelination and axonal degeneration. A growing number of reports confirms the role of miRNA molecules in regulation of neuroinflammation. miRNA can have a pro-inflammatory and anti-inflammatory effect and regulation of their expression can have a positive or negative effect on development of neuroinflammation. Further research of miRNA regulation mechanisms will give a better insight into the pathogenesis of multiple sclerosis, to identify miRNA that are suitable for the role of therapeutic targets