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Molecular Mechanisms in Demyelinating Disorders and Remyelination Strategies of the CNS

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 3136

Special Issue Editor

Dr. Paschalis Theotokis

E-Mail Website
Guest Editor
Department of Histology-Embryology, School of Medicine, Aristotle University of Thessaloniki, 54655 Thessaloniki, Greece
Interests: neuroscience; multiple sclerosis; experimental autoimmune encephalomyelitis; intrathecal transplantation; stem cell differentiation; immunohistopathology; in situ hybridization; electron microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A demyelinating disease is a pathological condition of the nervous system that negatively affects the structures and functions of the lipid sheaths that surround axons, ultimately interfering with nerve conduction. These lipid sheaths are lamellar membrane extensions of oligodendrocytes (OLs) in the central nervous system (CNS) and the Schwann cells in the peripheral nervous system (PNS). Myelinoclastic and leukodystrophic are the two categories into which demyelinating diseases have historically been divided. A typical, healthy myelin sheath is damaged in the first group as a result of a toxic, chemical, or autoimmune agent, while genetic-based aberrant myelin that is degenerated is present in the latter one, better known as dysmyelination.

Among the three main inflammatory-based CNS demyelinating diseases are multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and acute disseminated encephalomyelitis (ADEM). MS is the most prevalent one, affecting millions of people worldwide. Since the etiology of these diseases is still largely unknown, there is a need to establish new biomarkers and prioritize the development of experimental research, particularly at the molecular level. This is the second edition of a previous Special Issue, "Molecular Mechanisms in Demyelinating Disorders of the Central Nervous System", and we noted some remyelination strategies in this issue.

I hereby invite authors to submit original research, review articles, or commentaries on molecular mechanisms that shed light on to therapeutic strategies in demyelinating disorders and remyelination strategies of the CNS.

Dr. Paschalis Theotokis
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). 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

  • demyelination
  • molecular mechanisms
  • oligodendrocyte precursor cells
  • myelinogenesis
  • dysmyelination
  • lipid metabolism
  • microglia and macrophages
  • experimental autoimmune encephalomyelitis
  • biomarkers
  • remyelination

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Published Papers (3 papers)

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Research

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13 pages, 1748 KiB  
Article
Exploring the Gene Expression and Plasma Protein Levels of HSP90, HSP60, and GDNF in Multiple Sclerosis Patients and Healthy Controls
by Igor Sokolowski, Aleksandra Kucharska-Lusina, Elzbieta Miller, Tomasz Poplawski and Ireneusz Majsterek
Curr. Issues Mol. Biol. 2024, 46(10), 11668-11680; https://doi.org/10.3390/cimb46100693 - 19 Oct 2024
Viewed by 487
Abstract
Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by immune-mediated inflammation and neurodegeneration in the central nervous system (CNS). In this study; we aimed to investigate the gene expression and plasma protein levels of three neuroprotective genes—heat shock proteins (HSP90 and HSP60) [...] Read more.
Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by immune-mediated inflammation and neurodegeneration in the central nervous system (CNS). In this study; we aimed to investigate the gene expression and plasma protein levels of three neuroprotective genes—heat shock proteins (HSP90 and HSP60) and glial cell line-derived neurotrophic factor (GDNF)—in MS patients compared to healthy controls. Forty patients with relapsing-remitting MS and 40 healthy volunteers participated in this study. Gene expression was measured using reverse transcription quantitative real-time PCR, and protein levels were assessed via ELISA. The results showed a significant increase in HSP90 (1.7-fold) and HSP60 (2-fold) gene expression in MS patients compared to controls, along with corresponding increases in protein levels (1.5-fold for both HSP90 and HSP60). In contrast, GDNF gene expression and protein levels were significantly reduced in MS patients, with a 7-fold decrease in gene expression and a 1.6-fold reduction in protein levels. Notably, a non-linear relationship between GDNF gene expression and protein concentration was observed in MS patients, suggesting complex regulatory mechanisms influencing GDNF in the disease. The upregulation of HSP90 and HSP60 in MS highlights their roles in immune regulation and stress responses, while the reduction in GDNF indicates impaired neuroprotection. These findings suggest that HSP90, HSP60, and GDNF could serve as biomarkers for disease progression and as potential therapeutic targets in MS, offering promising avenues for future research and treatment development. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders and Remyelination Strategies of the CNS)
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15 pages, 2283 KiB  
Article
Immunomodulatory Effects of Anadenanthera colubrina Bark Extract in Experimental Autoimmune Encephalomyelitis
by Karla A. Ramos, Igor G. M. Soares, Larissa M. A. Oliveira, Mariana A. Braga, Pietra P. C. Soares, Gracimerio J. Guarneire, Elaine C. Scherrer, Fernando S. Silva, Nerilson M. Lima, Felipe A. La Porta, Teresinha de Jesus A. S. Andrade, Gagan Preet, Sandra B. R. Castro, Caio César S. Alves and Alessandra P. Carli
Curr. Issues Mol. Biol. 2024, 46(8), 8726-8740; https://doi.org/10.3390/cimb46080515 - 10 Aug 2024
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Abstract
This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite [...] Read more.
This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite profile, demonstrating a wide variety of polyphenols, such as flavonoids and phenolic acids. Various parameters were evaluated, such as clinical signs, cytokines, cellular profile, and histopathology in the central nervous system (CNS). The ethanolic extract of A. colubrina demonstrated significant positive effects attenuating the clinical signs and pathological processes associated with EAE. The beneficial effects of the extract treatment were evidenced by reduced levels of pro-inflammatory cytokines, such as IL1β, IL-6, IL-12, TNF, IFN-γ, and a notable decrease in several cell profiles, including CD8+, CD4+, CD4+IFN-γ, CD4+IL-17+, CD11c+MHC-II+, CD11+CD80+, and CD11+CD86+ in the CNS. In addition, histological analysis revealed fewer inflammatory infiltrates and demyelination sites in the spinal cord of mice treated with the extract compared to the control model group. These results showed, for the first time, that the ethanolic extract of A. colubrina exerts a modulatory effect on inflammatory processes, improving clinical signs in EAE, in the acute phase of the disease, which could be further explored as a possible therapeutic alternative. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders and Remyelination Strategies of the CNS)
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Review

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19 pages, 1658 KiB  
Review
Exploring the Therapeutic Potential: Bioactive Molecules and Dietary Interventions in Multiple Sclerosis Management
by Gabriele Tancreda, Silvia Ravera and Isabella Panfoli
Curr. Issues Mol. Biol. 2024, 46(6), 5595-5613; https://doi.org/10.3390/cimb46060335 - 3 Jun 2024
Viewed by 1129
Abstract
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It [...] Read more.
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It has been proposed that environmental factors, smoking, and dietary habits acting on a genetic susceptibility play a role in MS. Recent studies indicate that diet can significantly influence the onset and progression of MS. This review delves into the impact of natural bioactive molecules on MS development and explores the dietary interventions that hold promise in managing the disease. Dietary patterns, including ketogenic and Mediterranean diets, are discussed. Theories about the potential mechanistic associations beneath the noted effects are also proposed. Several dietary components and patterns demonstrated the potential for a significant impact on MS. However, extensive prospective clinical trials are necessary to fully understand the role of natural bioactive molecules as disease modifiers in MS. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders and Remyelination Strategies of the CNS)
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