A Comprehensive Exploration of the Transcriptomic Landscape in Multiple Sclerosis: A Systematic Review

Abstract

Multiple Sclerosis (MS) is, to date, an incurable disease of the nervous system characterized by demyelination. Several genetic mutations are associated with the disease but they are not able to explain all the diagnosticated cases. Thus, it is suggested that altered gene expression may play a role in human pathologies. In this review, we explored the role of the transcriptomic profile in MS to investigate the main altered biological processes and pathways involved in the disease. Herein, we focused our attention on RNA-seq methods that in recent years are producing a huge amount of data rapidly replacing microarrays, both with bulk and single-cells. The studies evidenced that different MS stages have specific molecular signatures and non-coding RNAs may play a key role in the disease. Sex-dependence was observed before and after treatments used to alleviate symptomatology activating different biological processes in a drug-dependent manner. New pathways, such as neddylation, were found deregulated in MS and inflammation was linked to neuron degeneration areas through spatial transcriptomics. It is evident that the use of RNA-seq in the study of complex pathologies, such as MS, is a valid strategy to shed light on new involved mechanisms.

Predicting glucocorticoid resistance in multiple sclerosis relapse via a whole blood transcriptomic analysis

“…Transcriptomic analysis of different cell types, fluids, or tissues of MS patients has already been performed 42 . In most studies, a dysregulation of the immune system has been observed 42,43 .…”

“…41 Transcriptomic analysis of different cell types, fluids, or tissues of MS patients has already been performed. 42 In most studies, a dysregulation of the immune system has been observed. 42,43 With hundreds of genes being differentially expressed in T cells and monocytes from patients with MS compared to healthy controls, 44 clinical implication of this data remains challenging.…”

RGS2-related non-coding interaction network modulates the NF-Kappa B signaling pathway in MS patients: a systems biology investigation

“…After 10-15 years, most RRMS patients develop Secondary Progressive MS (SPMS), which is characterized by ongoing neurological deterioration. In a small percentage of MS patients (about 15%), the disease can be progressive from the onset, which is known as Primary Progressive MS (PPMS) (11)(12)(13)(14).…”

“…CD20 + B cells are the most frequently seen in the early stages of the disease, while plasma blasts and plasma cells are the most prominent in the later stages. B cell engagement relates to not only antibody production, but also antigen presentation to T cells and modulation of T cells and myeloid cells function as a result of cytokine secretion (13,15,16) Long non-coding RNAs (lncRNAs) are vital contributors to intricate biological processes, and their presence in body uids, coupled with their speci c distribution in tissues, positions these biomolecules as potentially valuable candidates for diagnosing MS (17). Despite not being translated into proteins, these elements play essential roles in various physiological processes, including cellular differentiation, stress response, aging, cell growth, programmed cell death, and the regulation of gene transcription (18).…”

In Silico Analysis Highlights Potential Predictive Indicators Associated with Secondary Progressive Multiple Sclerosis

“…This sobering reality underscores the significance of exploring other components in the pathology of MS [ 12 ]. The use of transcriptomics data may provide helpful insights to better define MS etiopathogenesis [ 13 ]. To better elucidate the specific cellular mechanisms underlying SPMS compared to RRMS, and thus enable early identification of MS subtypes, we analyzed brain and blood expression datasets for SPMS compared to a group of healthy controls (HCs).…”