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New Mechanisms and Therapeutics in Multiple Sclerosis: A Comprehensive Approach
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New Mechanisms and Therapeutics in Multiple Sclerosis: A Comprehensive Approach

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 7825

Special Issue Editor

Dr. Emanuele D'Amico

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences, University of Foggia, 72100 Foggia, Italy
Interests: multiple sclerosis; motoneuron disease; neuroimmunology; demyelinating diseases; NMOSD

Special Issue Information

Dear Colleagues,

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system, leading to neurodegeneration and manifesting as a variety of symptoms. The available treatments for MS only slow the disease course, probably because the etiology and disease mechanisms are poorly understood. At present, due to the still-uncertain MS etiology involving the influence of environmental factors; the individual genetic predisposition; and the immunological, biochemical, and physiological settings of the individual, there is a need for biomarkers which help to improve diagnostic and prognostic accuracy.

Among them, microRNAs are small, single-stranded, non-coding RNAs that repress the expression of target genes via post-transcriptional mechanisms. Furthermore, the sustained inflammatory phase of the disease leads to ion-channel changes, chronic oxidative stress and metabolites accumulation.

Since IJMS is a journal of molecular science, submissions with biomolecular experiments are very much encouraged. A better understanding of the mechanisms underlying the development, evolution and treatment of multiple sclerosis will help to rationally identify better therapeutic targets for this difficult disease.

We warmly welcome submissions, including original papers and reviews, on these widely discussed topics.

Dr. Emanuele D'Amico
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

  • multiple sclerosis
  • molecular patterns
  • miRNAs
  • biochemical pathways
  • oxidative stress
  • mitochondrial DNA
  • genomic
  • proteomic

Published Papers (3 papers)

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Research

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21 pages, 1640 KiB  
Article
Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE
by Beatriz Gutiérrez-Miranda, Isabel Gallardo, Eleni Melliou, Isabel Cabero, Yolanda Álvarez, Marta Hernández, Prokopios Magiatis, Marita Hernández and María Luisa Nieto
Int. J. Mol. Sci. 2023, 24(5), 4977; https://doi.org/10.3390/ijms24054977 - 04 Mar 2023
Cited by 2 | Viewed by 2014
Abstract
Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In [...] Read more.
Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In both, MS and its preclinical model, the experimental autoimmune encephalomyelitis (EAE) gastrointestinal symptoms including “leaky gut” have been reported. Oleacein (OLE), a phenolic compound from extra virgin olive oil or olive leaves, harbors a wide range of therapeutic properties. Previously, we showed OLE effectiveness preventing motor defects and inflammatory damage of CNS tissues on EAE mice. The current studies examine its potential protective effects on intestinal barrier dysfunction using MOG35-55-induced EAE in C57BL/6 mice. OLE decreased EAE-induced inflammation and oxidative stress in the intestine, preventing tissue injury and permeability alterations. OLE protected from EAE-induced superoxide anion and accumulation of protein and lipid oxidation products in colon, also enhancing its antioxidant capacity. These effects were accompanied by reduced colonic IL-1β and TNFα levels in OLE-treated EAE mice, whereas the immunoregulatory cytokines IL-25 and IL-33 remained unchanged. Moreover, OLE protected the mucin-containing goblet cells in colon and the serum levels of iFABP and sCD14, markers that reflect loss of intestinal epithelial barrier integrity and low-grade systemic inflammation, were significantly reduced. These effects on intestinal permeability did not draw significant differences on the abundance and diversity of gut microbiota. However, OLE induced an EAE-independent raise in the abundance of Akkermansiaceae family. Consistently, using Caco-2 cells as an in vitro model, we confirmed that OLE protected against intestinal barrier dysfunction induced by harmful mediators present in both EAE and MS. This study proves that the protective effect of OLE in EAE also involves normalizing the gut alterations associated to the disease. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Multiple Sclerosis: A Comprehensive Approach)
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Review

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21 pages, 3770 KiB  
Review
The State of the Art of Pediatric Multiple Sclerosis
by Raluca Ioana Teleanu, Adelina-Gabriela Niculescu, Oana Aurelia Vladacenco, Eugenia Roza, Radu-Stefan Perjoc and Daniel Mihai Teleanu
Int. J. Mol. Sci. 2023, 24(9), 8251; https://doi.org/10.3390/ijms24098251 - 04 May 2023
Cited by 4 | Viewed by 2185
Abstract
Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around the age of 20–30 years. Still, in recent years, MS has been increasingly recognized among the pediatric population, being characterized by several peculiar features compared [...] Read more.
Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around the age of 20–30 years. Still, in recent years, MS has been increasingly recognized among the pediatric population, being characterized by several peculiar features compared to adult-onset disease. Unfortunately, the etiology and disease mechanisms are poorly understood, rendering the already limited MS treatment options with uncertain efficacy and safety in pediatric patients. Thus, this review aims to shed some light on the progress in MS therapeutic strategies specifically addressed to children and adolescents. In this regard, the present paper briefly discusses the etiology, risk factors, comorbidities, and diagnosis possibilities for pediatric-onset MS (POMS), further moving to a detailed presentation of current treatment strategies, recent clinical trials, and emerging alternatives. Particularly, promising care solutions are indicated, including new treatment formulations, stem cell therapies, and cognitive training methods. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Multiple Sclerosis: A Comprehensive Approach)
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16 pages, 722 KiB  
Review
Mechanisms of Demyelination and Remyelination Strategies for Multiple Sclerosis
by Xinda Zhao and Claire Jacob
Int. J. Mol. Sci. 2023, 24(7), 6373; https://doi.org/10.3390/ijms24076373 - 28 Mar 2023
Cited by 2 | Viewed by 3240
Abstract
All currently licensed medications for multiple sclerosis (MS) target the immune system. Albeit promising preclinical results demonstrated disease amelioration and remyelination enhancement via modulating oligodendrocyte lineage cells, most drug candidates showed only modest or no effects in human clinical trials. This might be [...] Read more.
All currently licensed medications for multiple sclerosis (MS) target the immune system. Albeit promising preclinical results demonstrated disease amelioration and remyelination enhancement via modulating oligodendrocyte lineage cells, most drug candidates showed only modest or no effects in human clinical trials. This might be due to the fact that remyelination is a sophistically orchestrated process that calls for the interplay between oligodendrocyte lineage cells, neurons, central nervous system (CNS) resident innate immune cells, and peripheral immune infiltrates and that this process may somewhat differ in humans and rodent models used in research. To ensure successful remyelination, the recruitment and activation/repression of each cell type should be regulated in a highly organized spatio–temporal manner. As a result, drug candidates targeting one single pathway or a single cell population have difficulty restoring the optimal microenvironment at lesion sites for remyelination. Therefore, when exploring new drug candidates for MS, it is instrumental to consider not only the effects on all CNS cell populations but also the optimal time of administration during disease progression. In this review, we describe the dysregulated mechanisms in each relevant cell type and the disruption of their coordination as causes of remyelination failure, providing an overview of the complex cell interplay in CNS lesion sites. Full article
(This article belongs to the Special Issue New Mechanisms and Therapeutics in Multiple Sclerosis: A Comprehensive Approach)
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