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Molecular Mechanisms in Demyelinating Disorders of the Central Nervous System

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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 26517

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Guest Editor
1. Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece
2. Laboratory of Histology and Embryology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: neuroscience; multiple sclerosis; experimental autoimmune encephalomyelitis; intrathecal transplantation; stem cell differentiation; immunohistopathology; in situ hybridization; electron microscopy
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Special Issue Information

Dear Colleagues,

A demyelinating disease is a pathological condition of the nervous system that negatively affects the structure and function of the lipid sheath that surround axons, ultimately interfering with the 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 etiology of these diseases is still largely unknown, there’s a need to establish new biomarkers and prioritize the development of experimental research, particularly in the molecular level. I hereby invite authors to submit original research, review articles or commentaries on molecular mechanisms that shed light to therapeutic strategies in demyelinating disorders of the CNS.

Dr. Paschalis Theotokis
Guest Editor

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Keywords

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

Published Papers (12 papers)

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Editorial

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3 pages, 181 KiB  
Editorial
Exploring Myelin Dynamics in Demyelinating Disorders at the Molecular Level
by Paschalis Theotokis
Curr. Issues Mol. Biol. 2024, 46(3), 1754-1756; https://doi.org/10.3390/cimb46030114 - 26 Feb 2024
Cited by 1 | Viewed by 593
Abstract
Investigating the subtle molecular mechanisms underlying demyelinating disorders of the central nervous system (CNS) is pivotal in advancing therapeutic strategies and improving patient outcomes [...] Full article

Research

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14 pages, 1404 KiB  
Article
Testosterone Inhibits Secretion of the Pro-Inflammatory Chemokine CXCL1 from Astrocytes
by Malgorzata Turniak-Kusy, Maciej Studzian, Piotr Szpakowski, Piotr Kuchta, Kaja Smietanka, Claudia Mattern, Lukasz Pulaski and Bartosz Bielecki
Curr. Issues Mol. Biol. 2024, 46(3), 2105-2118; https://doi.org/10.3390/cimb46030135 - 06 Mar 2024
Viewed by 530
Abstract
Astrocytes play an important role in the regulation of the inflammatory response in the CNS, e.g., in demyelinating diseases. Since the chemokine CXCL1 is known to be secreted by astrocytes and to have a pro-inflammatory effect on immune cells in the CNS, we [...] Read more.
Astrocytes play an important role in the regulation of the inflammatory response in the CNS, e.g., in demyelinating diseases. Since the chemokine CXCL1 is known to be secreted by astrocytes and to have a pro-inflammatory effect on immune cells in the CNS, we verified the effect of testosterone on its secretion in vitro (in the astrocytic cell line DI TNC1). Testosterone reduced the increase in CXCL1 production caused by the pro-inflammatory agent lysophosphatidylcholine and restored the basal production level of CXCL1. The androgen receptor (present and functional in the studied cell line) was strongly suggested to mediate this effect—its non-steroid ligand flutamide exerted an agonist-like effect, mimicking the activity of testosterone itself on CXCL1 secretion. This novel mechanism has important implications for the known immunomodulatory effect of testosterone and potentially other androgenic hormones. It provides a potential explanation on the molecular level and shows that astrocytes are important players in inflammatory homeostasis in the CNS and its hormonal regulation. Therefore, it suggests new directions for the development of the therapeutic intervention. Full article
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24 pages, 5553 KiB  
Article
Overexpression of OLIG2 and MYT1L Transcription Factors Enhance the Differentiation Potential of Human Mesenchymal Stem Cells into Oligodendrocytes
by Ifrah Fahim, Aisha Ishaque, Faiza Ramzan, Shamsul Azlin Bin Ahmad Shamsuddin, Anwar Ali, Asmat Salim and Irfan Khan
Curr. Issues Mol. Biol. 2023, 45(5), 4100-4123; https://doi.org/10.3390/cimb45050261 - 07 May 2023
Viewed by 1715
Abstract
Background: Demyelinating diseases represent a broad spectrum of disorders and are characterized by the loss of specialized glial cells (oligodendrocytes), which eventually leads to neuronal degeneration. Stem cell-based regenerative approaches provide therapeutic options to regenerate demyelination-induced neurodegeneration. Objectives: The current study aims to [...] Read more.
Background: Demyelinating diseases represent a broad spectrum of disorders and are characterized by the loss of specialized glial cells (oligodendrocytes), which eventually leads to neuronal degeneration. Stem cell-based regenerative approaches provide therapeutic options to regenerate demyelination-induced neurodegeneration. Objectives: The current study aims to explore the role of oligodendrocyte-specific transcription factors (OLIG2 and MYT1L) under suitable media composition to facilitate human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) differentiation toward oligodendrocyte for their potential use to treat demyelinating disorders. Methodology: hUC-MSCs were isolated, cultured, and characterized based on their morphological and phenotypic characteristics. hUC-MSCs were transfected with OLIG2 and MYT1L transcription factors individually and in synergistic (OLIG2 + MYT1L) groups using a lipofectamine-based transfection method and incubated under two different media compositions (normal and oligo induction media). Transfected hUC-MSCs were assessed for lineage specification and differentiation using qPCR. Differentiation was also analyzed via immunocytochemistry by determining the expression of oligodendrocyte-specific proteins. Results: All the transfected groups showed significant upregulation of GFAP and OLIG2 with downregulation of NES, demonstrating the MSC commitment toward the glial lineage. Transfected groups also presented significant overexpression of oligodendrocyte-specific markers (SOX10, NKX2.2, GALC, CNP, CSPG4, MBP, and PLP1). Immunocytochemical analysis showed intense expression of OLIG2, MYT1L, and NG2 proteins in both normal and oligo induction media after 3 and 7 days. Conclusions: The study concludes that OLIG2 and MYT1L have the potential to differentiate hUC-MSCs into oligodendrocyte-like cells, which is greatly facilitated by the oligo induction medium. The study may serve as a promising cell-based therapeutic strategy against demyelination-induced neuronal degeneration. Full article
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13 pages, 1931 KiB  
Article
Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses
by Dariush Haghmorad, Bahman Yousefi, Majid Eslami, Ali Rashidy-Pour, Mahdieh Tarahomi, Maryam Jadid Tavaf, Azita Soltanmohammadi, Simin Zargarani, Aleksandr Kamyshnyi and Valentyn Oksenych
Curr. Issues Mol. Biol. 2022, 44(11), 5728-5740; https://doi.org/10.3390/cimb44110388 - 18 Nov 2022
Cited by 2 | Viewed by 2466
Abstract
Multiple Sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral [...] Read more.
Multiple Sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group, received PBS orally; prevention group, oral administration of MOG35–55 two weeks before EAE induction; treatment group, oral administration of MOG35–55 after EAE induction). MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, and reduction in pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells. Full article
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17 pages, 3062 KiB  
Article
Pro-Inflammatory and Pro-Apoptotic Effects of the Non-Protein Amino Acid L-Azetidine-2-Carboxylic Acid in BV2 Microglial Cells
by Jordan Allan Piper, Margo Iris Jansen, Sarah Thomas Broome, Kenneth J. Rodgers, Giuseppe Musumeci and Alessandro Castorina
Curr. Issues Mol. Biol. 2022, 44(10), 4500-4516; https://doi.org/10.3390/cimb44100308 - 28 Sep 2022
Cited by 2 | Viewed by 1835
Abstract
L-Azetidine-2-carboxylic acid (AZE) is a toxic non-protein coding amino acid (npAA) that is highly abundant in sugar and table beets. Due to its structural similarity with the amino acid L-proline, AZE can evade the editing process during protein assembly in eukaryotic cells and [...] Read more.
L-Azetidine-2-carboxylic acid (AZE) is a toxic non-protein coding amino acid (npAA) that is highly abundant in sugar and table beets. Due to its structural similarity with the amino acid L-proline, AZE can evade the editing process during protein assembly in eukaryotic cells and be misincorporated into L-proline-rich proteins, potentially causing protein misfolding and other detrimental effects to cells. In this study, we sought to determine if AZE treatment triggered pro-inflammatory and pro-apoptotic responses in BV2 microglial cells. BV2 microglial cells exposed to AZE at increasing concentrations (0–2000 µM) at 0, 3, 6, 12 and 24 h were assayed for cell viability (MTT) and nitric oxide release (Griess assay). Annexin V-FITC/propidium iodide (PI) staining was used to assess apoptosis. Real-time qPCR, Western blot and immunocytochemistry were used to interrogate relevant pro- and anti-inflammatory and other molecular targets of cell survival response. AZE (at concentrations > 1000 µM) significantly reduced cell viability, increased BAX/Bcl2 ratio and caused cell death. Results were mirrored by a robust increase in nitric oxide release, percentage of activated/polarised cells and expression of pro-inflammatory markers (IL-1β, IL-6, NOS2, CD68 and MHC-2a). Additionally, we found that AZE induced the expression of the extracellular matrix degrading enzyme matrix metalloproteinase 9 (MMP-9) and brain derived neurotrophic factor (BDNF), two critical regulators of microglial motility and structural plasticity. Collectively, these data indicate that AZE-induced toxicity is associated with increased pro-inflammatory activity and reduced survival in BV2 microglia. This evidence may prompt for an increased monitoring of AZE consumption by humans. Full article
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15 pages, 1710 KiB  
Article
Basic Analysis of the Cerebrospinal Fluid: An Important Framework for Laboratory Diagnostics of the Impairment of the Central Nervous System
by Petr Kelbich, Karel Hrach, Jan Spicka, Petr Vachata, Tomas Radovnicky, Eva Hanuljakova and Jan Krejsek
Curr. Issues Mol. Biol. 2022, 44(8), 3666-3680; https://doi.org/10.3390/cimb44080251 - 14 Aug 2022
Viewed by 2473
Abstract
Laboratory analysis of basic cerebrospinal fluid (CSF) parameters is considered as essential for any CSF evaluation. It can provide rapidly very valuable information about the status of the central nervous system (CNS). Our retrospective study evaluated parameters of basic CSF analysis in cases [...] Read more.
Laboratory analysis of basic cerebrospinal fluid (CSF) parameters is considered as essential for any CSF evaluation. It can provide rapidly very valuable information about the status of the central nervous system (CNS). Our retrospective study evaluated parameters of basic CSF analysis in cases of either infectious or non-infectious CNS involvement. Neutrophils are effector cells of innate immunity. Predominance of neutrophils was found in 98.2% of patients with purulent inflammation in CNS. Lymphocytes are cellular substrate of adaptive immunity. We found their predominance in 94.8% of patients with multiple sclerosis (MS), 66.7% of patients with tick-borne encephalitis (TBE), 92.2% of patients with neuroborreliosis, 83.3% of patients with inflammatory response with oxidative burst of macrophages in CNS and 75.0% of patients with malignant infiltration of meninges (MIM). The simultaneous assessment of aerobic and anaerobic metabolism in CSF using the coefficient of energy balance (KEB) allows us to specify the type of inflammation in CNS. We found predominantly aerobic metabolism (KEB > 28.0) in 100.0% CSF of patients with normal CSF findings and in 92.8% CSF of patients with MS. Predominant faintly anaerobic metabolism (28.0 > KEB > 20.0) in CSF was found in 71.8% patients with TBE and in 64.7% patients with neuroborreliosis. Strong anaerobic metabolism (KEB < 10.0) was found in the CSF of 99.1% patients with purulent inflammation, 100.0% patients with inflammatory response with oxidative burst of macrophages and in 80.6% patients with MIM. Joint evaluation of basic CSF parameters provides sufficient information about the immune response in the CSF compartment for rapid and reliable diagnosis of CNS involvement. Full article
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Review

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23 pages, 1818 KiB  
Review
The Roles of Caloric Restriction Mimetics in Central Nervous System Demyelination and Remyelination
by Despoina Kaffe, Stefanos Ioannis Kaplanis and Domna Karagogeos
Curr. Issues Mol. Biol. 2023, 45(12), 9526-9548; https://doi.org/10.3390/cimb45120596 - 27 Nov 2023
Viewed by 1541
Abstract
The dysfunction of myelinating glial cells, the oligodendrocytes, within the central nervous system (CNS) can result in the disruption of myelin, the lipid-rich multi-layered membrane structure that surrounds most vertebrate axons. This leads to axonal degeneration and motor/cognitive impairments. In response to demyelination [...] Read more.
The dysfunction of myelinating glial cells, the oligodendrocytes, within the central nervous system (CNS) can result in the disruption of myelin, the lipid-rich multi-layered membrane structure that surrounds most vertebrate axons. This leads to axonal degeneration and motor/cognitive impairments. In response to demyelination in the CNS, the formation of new myelin sheaths occurs through the homeostatic process of remyelination, facilitated by the differentiation of newly formed oligodendrocytes. Apart from oligodendrocytes, the two other main glial cell types of the CNS, microglia and astrocytes, play a pivotal role in remyelination. Following a demyelination insult, microglia can phagocytose myelin debris, thus permitting remyelination, while the developing neuroinflammation in the demyelinated region triggers the activation of astrocytes. Modulating the profile of glial cells can enhance the likelihood of successful remyelination. In this context, recent studies have implicated autophagy as a pivotal pathway in glial cells, playing a significant role in both their maturation and the maintenance of myelin. In this Review, we examine the role of substances capable of modulating the autophagic machinery within the myelinating glial cells of the CNS. Such substances, called caloric restriction mimetics, have been shown to decelerate the aging process by mitigating age-related ailments, with their mechanisms of action intricately linked to the induction of autophagic processes. Full article
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26 pages, 7410 KiB  
Review
Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels
by Dimitar Tonev and Albena Momchilova
Curr. Issues Mol. Biol. 2023, 45(10), 7749-7774; https://doi.org/10.3390/cimb45100489 - 25 Sep 2023
Cited by 1 | Viewed by 1030
Abstract
Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes [...] Read more.
Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments. Full article
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20 pages, 1640 KiB  
Review
Origin and Emergence of Microglia in the CNS—An Interesting (Hi)story of an Eccentric Cell
by Iasonas Dermitzakis, Maria Eleni Manthou, Soultana Meditskou, Marie-Ève Tremblay, Steven Petratos, Lida Zoupi, Marina Boziki, Evangelia Kesidou, Constantina Simeonidou and Paschalis Theotokis
Curr. Issues Mol. Biol. 2023, 45(3), 2609-2628; https://doi.org/10.3390/cimb45030171 - 22 Mar 2023
Cited by 6 | Viewed by 4297
Abstract
Microglia belong to tissue-resident macrophages of the central nervous system (CNS), representing the primary innate immune cells. This cell type constitutes ~7% of non-neuronal cells in the mammalian brain and has a variety of biological roles integral to homeostasis and pathophysiology from the [...] Read more.
Microglia belong to tissue-resident macrophages of the central nervous system (CNS), representing the primary innate immune cells. This cell type constitutes ~7% of non-neuronal cells in the mammalian brain and has a variety of biological roles integral to homeostasis and pathophysiology from the late embryonic to adult brain. Its unique identity that distinguishes its “glial” features from tissue-resident macrophages resides in the fact that once entering the CNS, it is perennially exposed to a unique environment following the formation of the blood–brain barrier. Additionally, tissue-resident macrophage progenies derive from various peripheral sites that exhibit hematopoietic potential, and this has resulted in interpretation issues surrounding their origin. Intensive research endeavors have intended to track microglial progenitors during development and disease. The current review provides a corpus of recent evidence in an attempt to disentangle the birthplace of microglia from the progenitor state and underlies the molecular elements that drive microgliogenesis. Furthermore, it caters towards tracking the lineage spatiotemporally during embryonic development and outlining microglial repopulation in the mature CNS. This collection of data can potentially shed light on the therapeutic potential of microglia for CNS perturbations across various levels of severity. Full article
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28 pages, 1156 KiB  
Review
Multiple Sclerosis: Inflammatory and Neuroglial Aspects
by Giulio Papiri, Giordano D’Andreamatteo, Gabriella Cacchiò, Sonila Alia, Mauro Silvestrini, Cristina Paci, Simona Luzzi and Arianna Vignini
Curr. Issues Mol. Biol. 2023, 45(2), 1443-1470; https://doi.org/10.3390/cimb45020094 - 08 Feb 2023
Cited by 13 | Viewed by 2652
Abstract
Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease’s natural history [...] Read more.
Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease’s natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells. Full article
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21 pages, 1121 KiB  
Review
Optic Neuritis in Multiple Sclerosis—A Review of Molecular Mechanisms Involved in the Degenerative Process
by Manuela Andreea Ciapă, Delia Lidia Șalaru, Cristian Stătescu, Radu Andy Sascău and Camelia Margareta Bogdănici
Curr. Issues Mol. Biol. 2022, 44(9), 3959-3979; https://doi.org/10.3390/cimb44090272 - 02 Sep 2022
Cited by 7 | Viewed by 2488
Abstract
Multiple sclerosis is a central nervous system inflammatory demyelinating disease with a wide range of clinical symptoms, ocular involvement being frequently marked by the presence of optic neuritis (ON). The emergence and progression of ON in multiple sclerosis is based on various pathophysiological [...] Read more.
Multiple sclerosis is a central nervous system inflammatory demyelinating disease with a wide range of clinical symptoms, ocular involvement being frequently marked by the presence of optic neuritis (ON). The emergence and progression of ON in multiple sclerosis is based on various pathophysiological mechanisms, disease progression being secondary to inflammation, demyelination, or axonal degeneration. Early identification of changes associated with axonal degeneration or further investigation of the molecular processes underlying remyelination are current concerns of researchers in the field in view of the associated therapeutic potential. This article aims to review and summarize the scientific literature related to the main molecular mechanisms involved in defining ON as well as to analyze existing data in the literature on remyelination strategies in ON and their impact on long-term prognosis. Full article
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30 pages, 1795 KiB  
Review
Developmental Cues and Molecular Drivers in Myelinogenesis: Revisiting Early Life to Re-Evaluate the Integrity of CNS Myelin
by Iasonas Dermitzakis, Maria Eleni Manthou, Soultana Meditskou, Dimosthenis Miliaras, Evangelia Kesidou, Marina Boziki, Steven Petratos, Nikolaos Grigoriadis and Paschalis Theotokis
Curr. Issues Mol. Biol. 2022, 44(7), 3208-3237; https://doi.org/10.3390/cimb44070222 - 19 Jul 2022
Cited by 8 | Viewed by 3450
Abstract
The mammalian central nervous system (CNS) coordinates its communication through saltatory conduction, facilitated by myelin-forming oligodendrocytes (OLs). Despite the fact that neurogenesis from stem cell niches has caught the majority of attention in recent years, oligodendrogenesis and, more specifically, the molecular underpinnings behind [...] Read more.
The mammalian central nervous system (CNS) coordinates its communication through saltatory conduction, facilitated by myelin-forming oligodendrocytes (OLs). Despite the fact that neurogenesis from stem cell niches has caught the majority of attention in recent years, oligodendrogenesis and, more specifically, the molecular underpinnings behind OL-dependent myelinogenesis, remain largely unknown. In this comprehensive review, we determine the developmental cues and molecular drivers which regulate normal myelination both at the prenatal and postnatal periods. We have indexed the individual stages of myelinogenesis sequentially; from the initiation of oligodendrocyte precursor cells, including migration and proliferation, to first contact with the axon that enlists positive and negative regulators for myelination, until the ultimate maintenance of the axon ensheathment and myelin growth. Here, we highlight multiple developmental pathways that are key to successful myelin formation and define the molecular pathways that can potentially be targets for pharmacological interventions in a variety of neurological disorders that exhibit demyelination. Full article
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