Abstract
Simple SummaryIn this study, we investigated the effect of microRNAs on the expression level of neuroprotective proteins, heat shock proteins, and sirtuin in peripheral blood mononuclear cells in the development of multiple sclerosis. Our results show that the gene expression of neurotrophins, heat shock proteins, SIRT1, and miRNAs by the immune cells of MS is d changed. A decrease in the expression of the BDNF and SIRT1 genes and an increase in the expression of miR-132-3p, miR-34a, and miR-132 in PBMCs may indicate an inhibition of the neuroprotective function of these cells, which may be associated with the transition of the immune system towards inflammation in the development of multiple sclerosis.Multiple sclerosis (MS) is a demyelinating disease characterized by chronic inflammation of the central nervous system, in which many factors can act together to influence disease susceptibility and progression. To date, the exact cause of MS is still unclear, but it is believed to result from an abnormal response of the immune system to one or more myelin antigens that develops in genetically susceptible individuals after their exposure to a, as yet undefined, causal agent. In our study, we assessed the effect of microRNAs on the expression level of neuroprotective proteins, including neurotrophins (BDNF and NT4/5), heat shock proteins (HSP70 and HSP27), and sirtuin (SIRT1) in peripheral blood mononuclear cells in the development of multiple sclerosis. The analysis of dysregulation of miRNA levels and the resulting changes in target mRNA/protein expression levels could contribute to a better understanding of the etiology of multiple sclerosis, as well as new alternative methods of diagnosis and treatment of this disease. The aim of this study was to find a link between neurotrophins (BDNF and NT4), SIRT1, heat shock proteins (HSP27 and HSP27), and miRNAs that are involved in the development of multiple sclerosis. The analysis of the selected miRNAs showed a negative correlation of SIRT1 with miR-132 and miR-34a and of BDNF with 132-3p in PBMCs, which suggests that the miRNAs we selected may regulate the expression level of the studied genes.
Highlights
IntroductionMultiple sclerosis (MS) is a serious neurological disorder affecting young Caucasian individuals, especially women, usually with an age of onset at 18–40 years
12 miRNAs that can regulate the expression of brainderived neurotrophic factor (BDNF) genes, neurotrophin 4/5 (NT4/5), SIRT1, HSP70, and HSP27
MiRNAs that can regulate the expression of BDNF genes, NT4/5, SIRT1, HSP70, and HSP27
Summary
Multiple sclerosis (MS) is a serious neurological disorder affecting young Caucasian individuals, especially women, usually with an age of onset at 18–40 years. Four clinical forms can be distinguished based on the clinical onset and disease progression: relapsingremitting (RRMS), the most frequent clinical form affecting approximately 80–85% of MS patients, secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). MS is not inherited, it has been shown that the probability of multiple sclerosis in a family member is higher (0.8–3% depending on the nature of the relationship with the patient and 25% in the case of identical twins) than in subjects without the MS history in their families (0.001%) [1]. The etiology and pathogenesis of MS remain elusive, but it is believed to result from an abnormal response of the immune system to one or more myelin antigens that develop in genetically susceptible individuals after their exposure to an as-yet undefined causal agent [2]
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