Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
4.9
Journals
IJMS
Special Issues
Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (20 October 2025) | Viewed by 6786

Special Issue Editor

Prof. Dr. Michael C. Levin

E-Mail Website
Guest Editor
Department of Medicine, Neurology Division, University of Saskatchewan, Saskatoon, SK S7N 0X8, Canada
Interests: neurology; neuroscience; multiple sclerosis; RNA-binding proteins; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue on “Insights in Multiple Sclerosis (MS) and Neuroimmunology”.

Neurodegeneration, defined as damage to neurons, oligodendrocytes, and axons, is now acknowledged to be the primary driver of disability in multiple sclerosis (MS) patients. Therefore, research into the mechanisms of neurodegeneration in MS has expanded over the past several years. Furthermore, with the development and implementation of more precise technologies, including sequencing and advanced imaging, we can more confidently define processes that cause damage to neurons, oligodendrocytes, and axons in MS.

For this Special Issue on ‘Insights in Multiple Sclerosis (MS) and Neuroimmunology’, we accept both reviews and original articles that explore the mechanisms of neurodegeneration, including those with an immunological mediator (i.e., macrophages, T-cells, B-cells, astrocytes, etc.). Reviews should highlight the most recent findings with regard to this topic, as well as emphasize novel approaches that are helping to advance this area of research. Original articles should demonstrate potential mechanisms of neurodegeneration, including damage to neurons, oligodendrocytes, and axons, in any MS models, including in vitro, in vivo, and in situ systems with a particular emphasis on immunological mediators. Original articles may also include potential therapies to combat neurodegeneration in MS.

This Special Issue is supervised by Prof. Dr. Michael C. Levin and assisted by Dr. Catherine Hutchinson. We warmly welcome the submission of short communications, original research articles, and review articles.

Prof. Dr. Michael C. Levin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegeneration
  • neuroimmunology
  • macrophage
  • T-cell
  • B-cell
  • antibody
  • neurons
  • oligodendrocytes
  • axon
  • axonal damage
  • cell death
  • multiple sclerosis

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 1024 KB  
Article
Modulation of Paraoxonase 1 Activity and Asymmetric Dimethylarginine by Immunomodulatory Therapies in Multiple Sclerosis
by Lilla Racz, Hajnalka Lorincz, Ildiko Seres, Laszlo Kardos, Gyorgy Paragh and Tunde Csepany
Int. J. Mol. Sci. 2025, 26(19), 9728; https://doi.org/10.3390/ijms26199728 - 6 Oct 2025
Viewed by 342
Abstract
Background: Neurodegeneration is present from the earliest stages of multiple sclerosis [MS], and oxidative stress together with mitochondrial dysfunction are key contributors to neuronal injury and disease progression. Objective: To investigate the role of the antioxidant enzyme paraoxonase 1 (PON1) and serum asymmetric [...] Read more.
Background: Neurodegeneration is present from the earliest stages of multiple sclerosis [MS], and oxidative stress together with mitochondrial dysfunction are key contributors to neuronal injury and disease progression. Objective: To investigate the role of the antioxidant enzyme paraoxonase 1 (PON1) and serum asymmetric dimethylarginine (ADMA) levels in MS across different disease subtypes and immunomodulatory treatments. Methods: Serum lipid levels and PON1 activity were measured and compared by disease subtype and treatment in a single-center MS cohort (N = 262; CIS = 10, RRMS = 208, PPMS = 19, SPMS = 25; 110 untreated, 152 treated) and in 91 healthy controls. ADMA levels were assessed in sera from 79 MS patients (19 untreated, 60 treated) and 31 age-matched controls. Results: Median serum paraoxonase (PON) and arylesterase (ARE) activity levels were 83.8 and 127.2 IU/L in MS patients versus 85.9 and 136.9 IU/L in controls, with no significant difference for PON (p = 0.191) but a significant reduction in ARE [p = 0.003]. PON activity differed significantly among disease subtypes (p = 0.023), with the highest levels in CIS. PON and ARE activity also varied across treatment groups (p = 0.038 and p = 0.034, respectively), with longitudinal analysis indicating a measurable effect of immunomodulatory therapy on PON activity at 10 years (p = 0.0136). Significant differences in enzyme activity were observed between untreated and interferon-treated patients (PON p = 0.0055, ARE p = 0.0001), with trends toward differences in ARE under natalizumab and fingolimod. ADMA levels were lower in MS patients than controls (p < 0.0001) and differed among treatment subgroups (natalizumab, dimethyl fumarate, glatiramer acetate, untreated RRMS). Conclusions: PON1 activity and ADMA levels differ between MS subgroups and under immunomodulatory treatments. Long-term therapy was associated with increased PON1 activity, while highly effective immunomodulators reduced ADMA levels. These changes may contribute to the treatment-related reduction in disease activity and attenuation of neurodegenerative processes in MS. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
►▼ Show Figures

Figure 1

10 pages, 1474 KB  
Article
Exploring the Prognostic Role of Neurofilaments and SEMA3A in Multiple Sclerosis Progression
by Zbyšek Pavelek, Ondřej Souček, Jan Krejsek, Ilona Součková, Andrea Popovičová, David Matyáš, Lukáš Sobíšek and Michal Novotný
Int. J. Mol. Sci. 2025, 26(17), 8750; https://doi.org/10.3390/ijms26178750 - 8 Sep 2025
Viewed by 784
Abstract
The transition from relapsing–remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is characterized by an increasing neurodegenerative component. Identifying biomarkers that distinguish these disease stages is crucial for early diagnosis and treatment optimization. This study aimed to compare serum levels of [...] Read more.
The transition from relapsing–remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is characterized by an increasing neurodegenerative component. Identifying biomarkers that distinguish these disease stages is crucial for early diagnosis and treatment optimization. This study aimed to compare serum levels of progranulin, interleukin-6 (IL-6), semaphorin 3A (SEMA3A), and neurofilaments between RRMS and SPMS patients and to investigate their correlation with clinical characteristics, including disability measured by the Expanded Disability Status Scale (EDSS). This observational study included 118 MS patients (63 RRMS and 55 SPMS). Serum biomarker levels were measured using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses included group comparisons using non-parametric tests and correlation analyses using Pearson’s correlation coefficient with multiple testing corrections. While demographic and clinical parameters significantly differed between groups (p < 0.001), biomarker levels showed no statistically significant differences (p > 0.05). However, in SPMS patients, SEMA3A correlated positively with neurofilaments (r = 0.359, p = 0.007), and progranulin correlated with IL-6 (r = 0.354, p = 0.008). No significant biomarker correlations with EDSS were found. Although absolute biomarker levels did not distinguish RRMS from SPMS, specific biomarker correlations may reflect processes relevant to disease progression and warrant further longitudinal validation. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
►▼ Show Figures

Figure 1

20 pages, 1676 KB  
Article
Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis
by Enric Monreal, José Ignacio Fernández-Velasco, Susana Sainz de la Maza, Mercedes Espiño, Noelia Villarrubia, Ernesto Roldán-Santiago, Yolanda Aladro, Juan Pablo Cuello, Lucía Ayuso-Peralta, Alexander Rodero-Romero, Juan Luís Chico-García, Fernando Rodríguez-Jorge, Ana Quiroga-Varela, Eulalia Rodríguez-Martín, Belén Pilo de la Fuente, Guillermo Martín-Ávila, María Luisa Martínez-Ginés, José Manuel García-Domínguez, Lluïsa Rubio, Sara Llufriu, Manuel Comabella, Xavier Montalban, Gary Álvarez-Bravo, José Luís Veiga-González, Jaime Masjuan, Lucienne Costa-Frossard and Luisa María Villaradd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(14), 6898; https://doi.org/10.3390/ijms26146898 - 18 Jul 2025
Viewed by 1215
Abstract
The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different [...] Read more.
The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB–positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB–negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
►▼ Show Figures

Figure 1

13 pages, 1914 KB  
Article
Profiling Blood-Based Neural Biomarkers and Cytokines in Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Using Single-Molecule Array Technology
by Insha Zahoor, Sajad Mir and Shailendra Giri
Int. J. Mol. Sci. 2025, 26(7), 3258; https://doi.org/10.3390/ijms26073258 - 1 Apr 2025
Cited by 4 | Viewed by 1211
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based analytes, including cytokines and neural biomarkers are the predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in [...] Read more.
Experimental autoimmune encephalomyelitis (EAE) is a preclinical animal model widely used to study multiple sclerosis (MS). Blood-based analytes, including cytokines and neural biomarkers are the predictors of neurodegeneration, disease activity, and disability in patients with MS. However, understudied confounding factors cause variation in reports on EAE across animal strains/studies, limiting the utility of these biomarkers for predicting disease activity. In this study, we investigated blood-based analyte profiles, including neural markers (NFL and GFAP) and cytokines (IL-6, IL-17, IL-12p70, IL-10, and TNF-α), in two clinically distinct EAE models: relapsing-remitting (RR)-EAE and chronic-EAE. Ultrasensitive single-molecule array technology (SIMOA, Quanterix) was used to profile the analytes in the blood plasma of mice at the acute, chronic, and progressive phases of disease. In both models, NFL was substantially increased during post-disease onset across all phases, with a pronounced increase observed in chronic-EAE. The leakage of GFAP into peripheral blood was also greater after disease onset in both EAE models, especially in the acute phase of chronic-EAE. Among all cytokines, only IL-10 had consistently lower levels in both EAE models throughout the course of disease. This study suggests NFL, GFAP, and IL-10 as potential translational predictors of disease activity in EAE, making them potential candidates as surrogate markers for the preclinical testing of therapeutic interventions in animal models of MS. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
►▼ Show Figures

Figure 1

Review

Jump to: Research

48 pages, 950 KB  
Review
Metabolomics in Multiple Sclerosis: Advances, Challenges, and Clinical Perspectives—A Systematic Review
by Jan Smusz, Patrycja Mojsak, Paulina Matys, Anna Mirończuk, Joanna Tarasiuk, Kamil Grubczak, Aleksandra Starosz, Jan Kochanowicz, Alina Kułakowska, Katarzyna Ruszczyńska and Katarzyna Kapica-Topczewska
Int. J. Mol. Sci. 2025, 26(18), 9207; https://doi.org/10.3390/ijms26189207 - 20 Sep 2025
Viewed by 909
Abstract
Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder marked by inflammation, demyelination, and neuronal loss within the central nervous system. Despite advances in diagnostics, current tools remain insufficiently sensitive and specific. Metabolomics has emerged as a promising approach to explore MS pathophysiology [...] Read more.
Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder marked by inflammation, demyelination, and neuronal loss within the central nervous system. Despite advances in diagnostics, current tools remain insufficiently sensitive and specific. Metabolomics has emerged as a promising approach to explore MS pathophysiology and discover novel biomarkers. This PRISMA-guided systematic review included 29 original studies using validated metabolomic techniques in adult patients with MS. Biological samples analyzed included serum, cerebrospinal fluid, and feces. Consistent metabolic alterations were identified across several pathways. The kynurenine pathway demonstrated a shift toward neurotoxic metabolites, alongside reductions in microbial-derived indoles, indicating inflammation and gut dysbiosis. Energy metabolism was impaired, with changes in glycolysis, tricarboxylic acid (TCA) cycle, and mitochondrial function. Lipid metabolism showed widespread dysregulation involving phospholipids, sphingolipids, endocannabinoids, and polyunsaturated fatty acids, some modulated by treatments such as ocrelizumab and interferon-β. Nitrogen metabolism was also affected, including amino acids, peptides, and nucleotides. Non-classical and xenobiotic metabolites, such as myo-inositol, further reflected host–microbiome–environment interactions. Several studies demonstrated the potential of metabolomics-based machine learning to distinguish MS subtypes. These findings highlight the value of metabolomics for biomarker discovery and support its integration into personalized therapeutic strategies in MS. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
►▼ Show Figures

Figure 1

37 pages, 2404 KB  
Review
From Molecules to Models: miRNAs and Advanced Human Platforms of Neurodegeneration and Repair in Multiple Sclerosis
by María Muñoz-San Martín, Lucía de la Guerra-Sasián, Gabriel Gárate, Jorge Madera, Andrea González-Suárez, Nadia C. Cavada-Bustamante, Vicente González-Quintanilla and Jennifer K. Dowling
Int. J. Mol. Sci. 2025, 26(17), 8740; https://doi.org/10.3390/ijms26178740 - 8 Sep 2025
Viewed by 1283
Abstract
Beyond the potential role of microRNAs (miRNAs) as biomarkers, their participation in different biological and pathological processes observed in multiple sclerosis (MS) such as neuroinflammation, neurodegeneration and remyelination, makes them suitable candidates for therapeutic applications in neurorepair. Most studies addressing this reparative approach [...] Read more.
Beyond the potential role of microRNAs (miRNAs) as biomarkers, their participation in different biological and pathological processes observed in multiple sclerosis (MS) such as neuroinflammation, neurodegeneration and remyelination, makes them suitable candidates for therapeutic applications in neurorepair. Most studies addressing this reparative approach have been carried out using in vitro or in vivo model systems. However, functional differences between murine and human cells within the central nervous system (CNS) have been described, and certain mechanisms are distinctive in humans. The development of human models to investigate therapeutic interventions in neurological conditions including MS should be a priority to avoid failures. In this review, we provide a comprehensive summary of the advances in reparative therapeutic strategies for MS, including miRNAs and human models. We also discuss their benefits, the likely challenges they face and comment on possible mitigation strategies. Full article
(This article belongs to the Special Issue Insights in Multiple Sclerosis (MS) and Neuroimmunology: 2nd Edition)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop