Multiple sclerosis (MS) is characterized by multifocal lesions, chronic inflammatory condition, and degenerative processes within the central nervous system (CNS) leading to demyelination. The most important cells involved in its pathogenesis are those which are CD4⁺, particularly proinflammatory Th1/Th17 and regulatory Treg. Signal cascades associated with CD4⁺ differentiation are regulated by microRNAs (miRNAs): short, single-stranded RNAs, responsible for negative regulation of gene expression at the posttranscriptional level. Several miRNAs have been consistently reported as showing dysregulated expression in MS, and their expression patterns may be elevated or decreased, depending on the function of specific miRNA in the immune system. Studies in MS patients indicate that, among others, miR-141, miR-200a, miR-155, miR-223, and miR-326 are upregulated, while miR-15b, miR-20b, miR-26a, and miR-30a are downregulated. Dysregulation of these miRNAs may contribute to the imbalance between pro- and anti-inflammatory processes, since their targets are associated with the regulation of Th1/Th17 and Treg cell differentiation. Highly expressed miRNAs can in turn suppress translation of key Th1/Th17 differentiation inhibitors. miRNA dysregulation may result from the impact of various factors at each stage of their biogenesis. Immature miRNA undergoes multistage transcriptional and posttranscriptional modifications; therefore, any protein involved in the processing of miRNAs can potentially lead to disturbances in their expression. Epigenetic modifications that have a direct impact on miRNA gene transcription may also play an important role.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS), which leads to disturbances in the conduction of nerve impulses, cognitive impairment, sensory and motor disturbances, as well as depressive symptoms. MS remains an incurable disease with a difficult diagnosis and unclear etiology. The aim of the analysis was to identify SNPs that may potentially be associated with an increased risk of developing MS. Blood samples were obtained from patients with MS (194 subjects) and age-matched healthy controls (188 subjects). The polymorphic variant frequencies of rs197412 T>C in GEMIN3, rs7813 G>A in GEMIN4, rs1106042 G>A in HIWI, rs10719 A>C in DROSHA, rs3742330 A>G in DICER1, rs11077 T>G in XPO5, rs14035 C>T in RAN, rs636832 G>A in AGO1 were determined in DNA using real-time PCR TaqMan^® SNP Genotyping Assay. Our findings indicate that the GG AGO1 rs636832 and AA GEMIN4 rs7813 genotypes were associated with an increased risk of MS. Although our findings provide a clearer understanding of the pathogenesis of MS, further investigations are needed to better understand their potential for the evaluation of other miRNA processing genes believed to be associated with MS etiology.

Multiple sclerosis is a chronic demyelinating disorder with an unclear etiology. A key role is thought to be played by Th17 cells and microRNAs associated with Th17, such as miR-155, miR-326 and miR-223. The present study compared the methylation and hydroxymethylation levels of CpG sites within promoters of these microRNA between MS patients and controls using PBMCs and analyzed their relationship with microRNA expression. Significant intergroup differences were found between the levels of 5-hmC within the CpG-1 miR-155 promoter and CpG within the miR-326 promoter; in addition, miR-155-5p and miR-223-3p expression was elevated in MS patients. Correlation analysis showed a positive relationship between the level of 5-hmC of CpG-2 in the miR-223 promoter and miR-223-3p level. As it is possible to pharmacologically modulate the level of epigenetic modifications, our findings cast light on the etiology of MS and support the development of more effective therapies.

Ostatnie badania mające na celu poznanie molekularnych mechanizmów chorób człowieka wskazują, iż w patogenezie wielu zaburzeń metabolicznych, włączając w to procesy zapalne, starzenie organizmu, a także nowotworowy oraz choroby neurodegeneracyjne, znaczącą rolę odgrywa stres ER, który jest związany z gromadzeniem się nieprawidłowo sfałdowanych białek w świetle ER. W odpowiedzi na stres ER indukowany jest szlak UPR, który może pełnić dwojaką rolę. Szlak UPR może przywracać homeostazę w obrębie ER poprzez degradację nieprawidłowych białek, hamowanie dalszej translacji i mobilizację białek opiekuńczych, ale może również promować apoptozę w warunkach przedłużającego się stresu ER. Szlak UPR rozgałęzia się na trzy odrębne ścieżki sygnałowe, w którym uczestniczą trzy receptory transmembranowe: PERK, IRE1 oraz ATF6. Najbardziej obiecująca dla rozwoju nowych terapii wielu schorzeń człowieka, a w szczególności chorób neurodegeneracyjnych oraz nowotworowych, jest ścieżka związana z PERK, której inhibicja wykazywała pozytywne efekty terapeutyczne zarówno w badaniach in vitro jak i in vivo.