International Journal of Molecular Sciences

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Special Issue Editors

Special Issue Information

Dear Colleagues,

Multiple sclerosis (MS) is one of the most common and invalidating neurological diseases, involving mainly young adults and for which a definitive cure is not yet available. Although identifying patients at high risk of disease activity and disability progression is still a major unmet need, scientific research has been particularly prolific in recent years. We have observed substantial progress in the knowledge about the immunopathogenesis of the disease, including but not limited to the EBV studies. The concept of progression independent of relapse “PIRA” has emerged as the hallmark of such a “Smouldering” disease, which has been linked with meningeal inflammation and chronic active lesions. Several biomarkers have been associated with these pathological processes, and the role of microglia is currently under investigation. This Special Issue aims to summarize the new immunopathological and therapeutic advances with a special interest in smouldering disease and disability progression. Original research articles, review articles, and short communications within (but not restricted to) the described research fields are welcome.

Dr. Massimiliano Calabrese
Dr. Massimiliano Di Filippo
Guest Editors

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Keywords

multiple sclerosis
meningeal inflammation
neurodegeneration
PIRA
smouldering disease
biomarkers
microglia

Published Papers (2 papers)

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Research

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16 pages, 2454 KiB

Open AccessArticle

Effect of Siponimod on Brain and Spinal Cord Imaging Markers of Neurodegeneration in the Theiler’s Murine Encephalomyelitis Virus Model of Demyelination

by Suyog Pol, Ravendra Dhanraj, Anissa Taher, Mateo Crever, Taylor Charbonneau, Ferdinand Schweser, Michael Dwyer and Robert Zivadinov

Int. J. Mol. Sci. 2023, 24(16), 12990; https://doi.org/10.3390/ijms241612990 - 20 Aug 2023

Viewed by 959

Abstract

Siponimod (Sp) is a Sphingosine 1-phosphate (S1P) receptor modulator, and it suppresses S1P- mediated autoimmune lymphocyte transport and inflammation. Theiler’s murine encephalomyelitis virus (TMEV) infection mouse model of multiple sclerosis (MS) exhibits inflammation-driven acute and chronic phases, spinal cord lesions, brain and spinal cord atrophy, and white matter injury. The objective of the study was to investigate whether Sp treatment could attenuate inflammation-induced pathology in the TMEV model by inhibiting microglial activation and preventing the atrophy of central nervous tissue associated with neurodegeneration. Clinical disability score (CDS), body weight (BW), and rotarod retention time measures were used to assess Sp’s impact on neurodegeneration and disease progression in 4 study groups of 102 animals, including 44 Sp-treated (SpT), 44 vehicle-treated, 6 saline-injected, and 8 age-matched healthy controls (HC). Next, 58 (22 SpT, 22 vehicle, 6 saline injected, and 8 HC) out of the 102 animals were further evaluated to assess the effect of Sp on brain region-specific and spinal cord volume changes, as well as microglial activation. Sp increased CDS and decreased BW and rotarod retention time in TMEV mice, but did not significantly affect most brain region volumes, except for lateral ventricle volume. Sp suppressed ventricular enlargement, suggesting reduced TMEV-induced inflammation in LV. No significant differences in spine volume changes were observed between Sp- and vehicle-treated animals, but there were differences between HC and TMEV groups, indicating TMEV-induced inflammation contributed to increased spine volume. Spine histology revealed no significant microglial density differences between groups in gray matter, but HC animals had higher type 1 morphology and lower type 2 morphology percentages in gray and white matter regions. This suggests that Sp did not significantly affect microglial density but may have modulated neuroinflammation in the spinal cord. Sp may have some effects on neuroinflammation and ventricular enlargement. However, it did not demonstrate a significant impact on neurodegeneration, spinal volume, or lesion volume in the TMEV mouse model. Further investigation is required to fully understand Sp’s effect on microglial activation and its relevance to the pathophysiology of MS. The differences between the current study and previous research using other MS models, such as EAE, highlight the differences in pathological processes in these two disease models. Full article

(This article belongs to the Special Issue Recent Progress and Perspectives in Multiple Sclerosis)

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Review

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34 pages, 1588 KiB

Open AccessReview

Multiple Sclerosis: Roles of miRNA, lcnRNA, and circRNA and Their Implications in Cellular Pathways

by Giovanni Luca Cipriano, Giovanni Schepici, Emanuela Mazzon and Ivan Anchesi

Int. J. Mol. Sci. 2024, 25(4), 2255; https://doi.org/10.3390/ijms25042255 - 13 Feb 2024

Viewed by 849

Abstract

Multiple sclerosis (MS) is a degenerative condition characterized by axonal damage and demyelination induced by autoreactive immune cells that occur in the Central Nervous System (CNS). The interaction between epigenetic changes and genetic factors can be widely involved in the onset, development, and progression of the disease. Although numerous efforts were made to discover new therapies able to prevent and improve the course of MS, definitive curative treatments have not been found yet. However, in recent years, it has been reported that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), acting as gene expression regulators, could be used as potential therapeutic targets or biomarkers to diagnose and fight MS. In this review, we discussed the role of miRNAs, lncRNAs, and circRNAs, as well as their expression level changes and signaling pathways that are related to preclinical and human MS studies. Hence, the investigation of ncRNAs could be important to provide additional information regarding MS pathogenesis as well as promote the discovery of new therapeutic strategies or biomarkers. Full article

(This article belongs to the Special Issue Recent Progress and Perspectives in Multiple Sclerosis)

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