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Cancer Immunology, Immunotherapy : CII Feb 2020Schwann cells are the principal glial cells of the peripheral nervous system which maintain neuronal homeostasis. Schwann cells support peripheral nerve functions and... (Review)
Review
Schwann cells are the principal glial cells of the peripheral nervous system which maintain neuronal homeostasis. Schwann cells support peripheral nerve functions and play a critical role in many pathological processes including injury-induced nerve repair, neurodegenerative diseases, infections, neuropathic pain and cancer. Schwann cells are implicated in a wide range of diseases due, in part, to their ability to interact and modulate immune cells. We discuss the accumulating examples of how Schwann cell regulation of the immune system initiates and facilitates the progression of various diseases. Furthermore, we highlight how Schwann cells may orchestrate an immunosuppressive tumor microenvironment by polarizing and modulating the activity of the dendritic cells.
Topics: Animals; Biomarkers; Disease Susceptibility; Humans; Immunomodulation; Myelin Sheath; Schwann Cells; Signal Transduction
PubMed: 31676924
DOI: 10.1007/s00262-019-02424-7 -
The Neuroscientist : a Review Journal... Feb 2012Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and... (Review)
Review
Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and its failure results in devastating demyelinating diseases. During development, both oligodendrocyte and Schwann cell precursors undergo a temporally well-defined series of molecular and structural changes, ultimately culminating in the cessation of proliferation and the elaboration of a highly complex myelin sheath. Recent studies have demonstrated a critical role of microRNAs (miRNAs) in the progression of oligodendrocyte and Schwann cell precursors to the myelinating state-depletion of miRNAs from either cell type results in an arrest in differentiation and lack of myelination. Furthermore, these studies have begun to elucidate the dynamic regulation of miRNA expression and the complexity of miRNA-mediated gene regulation during differentiation of myelinating cells. In this review, the authors highlight the recent understanding of functional links of miRNAs to regulatory networks for central and peripheral myelination, as well as perspectives on the role of miRNAs in demyelinating diseases.
Topics: Animals; Astrocytes; Axons; Cell Differentiation; Demyelinating Diseases; Gene Expression Regulation; Humans; Mice; Mice, Knockout; MicroRNAs; Myelin Sheath; Neurons; Oligodendroglia; Schwann Cells
PubMed: 21536841
DOI: 10.1177/1073858410392382 -
Frontiers in Bioscience (Scholar... Jan 2011In recent years increasing evidence is pointing toward white matter abnormalities in schizophrenia and other psychiatric disorders. The present paper will provide an... (Review)
Review
In recent years increasing evidence is pointing toward white matter abnormalities in schizophrenia and other psychiatric disorders. The present paper will provide an overview over the role of myelin in cognition and brain function, and its potential involvement in brain disorders. Furthermore, we will examine one particular experimental model for the study of dysmyelination, created by the administration of the toxin cuprizone. Cuprizone, a copper chelator, causes white matter abnormalities in rodents. The administration of cuprizone during specific developmental periods allows for the targeting of specific brain areas for dysmyelination. Thus, cuprizone can be used to study the pathogenesis and pathophysiology of myelin deficiencies in the central nervous system, and its effect on behaviors relevant to psychiatric disorders.
Topics: Animals; Biological Evolution; Copper; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Humans; Mice; Myelin Sheath; Oligodendroglia; Schizophrenia
PubMed: 21196354
DOI: 10.2741/s129 -
Neuroscience Sep 2014Myelination by oligodendrocytes is a highly specialized process that relies on intimate interactions between the axon and the oligodendrocytes. Astrocytes have an... (Review)
Review
Myelination by oligodendrocytes is a highly specialized process that relies on intimate interactions between the axon and the oligodendrocytes. Astrocytes have an important part in facilitating myelination in the CNS, however, comparatively less is known about how they affect myelination. This review therefore summarizes the literature and explores lingering questions surrounding differences between white matter and gray matter astrocytes, how astrocytes support myelination, how their dysfunction in pathological states contributes to myelin pathologies and how astrocytes may facilitate remyelination. We discuss how astrocytes in the white matter are specialized to promote myelination and myelin maintenance by clearance of extracellular ions and neurotransmitters and by secretion of pro-myelinating factors. Additionally, astrocyte-oligodendrocyte coupling via gap junctions is crucial for both myelin formation and maintenance, due to K(+) buffering and possibly metabolic support for oligodendrocytes via the panglial syncytium. Dysfunctional astrocytes aberrantly affect oligodendrocytes, as exemplified by a number of leukodystrophies in which astrocytic pathology is known as the direct cause of myelin pathology. Conversely, in primary demyelinating diseases, such as multiple sclerosis, astrocytes may facilitate remyelination. We suggest that specific manipulation of astrocytes could help prevent myelin pathologies and successfully restore myelin sheaths after demyelination.
Topics: Animals; Astrocytes; Gray Matter; Humans; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; White Matter
PubMed: 24231735
DOI: 10.1016/j.neuroscience.2013.10.050 -
Molecular Neurobiology Aug 2009Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin... (Review)
Review
Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeostasis. Cataloging the myelin proteome has been made possible by technical advances in the separation and mass spectrometric detection of proteins, also referred to as proteomics. This led to the identification of a large number of novel myelin-associated proteins, many of which represent low abundant components involved in catalytic activities, the cytoskeleton, vesicular trafficking, or cell adhesion. By mass spectrometry-based quantification, proteolipid protein and myelin basic protein constitute 17% and 8% of total myelin protein, respectively, suggesting that their abundance was previously overestimated. As the biochemical profile of myelin-associated proteins is highly reproducible, differential proteome analyses can be applied to material isolated from patients or animal models of myelin-related diseases such as multiple sclerosis and leukodystrophies.
Topics: Animals; Demyelinating Diseases; Humans; Myelin Proteins; Myelin Sheath; Proteolipids; Proteomics
PubMed: 19452287
DOI: 10.1007/s12035-009-8071-2 -
Neurotherapeutics : the Journal of the... Jan 2013Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin... (Review)
Review
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin and axons. All therapeutics used to treat MS have been developed to target an overactive immune response, with aims to reduce disease activity. Chronic demyelinated axons are further prone to irreversible damage and death, and it is imperative that new therapies address this critical issue. Remyelination, the generation of new myelin in the adult nervous system, is an endogenous repair mechanism that restores function of denuded axons and delays their deterioration. Although remyelination can be extensive in some patients, the majority of cases limit repair only to the acute phase of disease. A significant current drive in new MS therapeutics is to identify targets that can promote remyelination by boosting endogenous oligodendrocyte precursor cells to form new myelin. Also, a number of inhibitory pathways have been identified in chronic MS lesions that prevent oligodendrocyte precursor cells from being properly recruited to demyelinated lesions or interfere with their differentiation to myelin-forming oligodendrocytes. In this review, we introduce the phenomenon of remyelination from the view of experimental models and studies in MS patients, describe a potential role in remyelination for currently available MS mediations, and discuss many avenues that are being actively studied to promote remyelination. The next frontier in MS therapeutics will supplement immunomodulation with agents that directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.
Topics: Animals; Demyelinating Diseases; Humans; Immunologic Factors; Multiple Sclerosis; Myelin Sheath
PubMed: 23070731
DOI: 10.1007/s13311-012-0152-7 -
Nature Reviews. Neurology May 2010The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of... (Review)
Review
The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of diseases, notably multiple sclerosis (MS). In MS, demyelination is associated with progressive axonal damage, which determines the level of patient disability. The few treatments that are available for combating myelin damage in MS and related disorders, which largely comprise anti-inflammatory drugs, only show limited efficacy in subsets of patients. More-effective treatment of myelin disorders will probably be accomplished by early intervention with combinatorial therapies that target inflammation and other processes-for example, signaling pathways that promote remyelination. Indeed, evidence suggests that such pathways might be impaired in pathology and, hence, contribute to the failure of remyelination in such diseases. In this article, we review the molecular basis of signaling pathways that regulate myelination in the CNS and PNS, with a focus on signals that affect differentiation of myelinating glia. We also discuss factors such as extracellular molecules that act as modulators of these pathways. Finally, we consider the few preclinical and clinical trials of agents that augment this signaling.
Topics: Animals; Anti-Inflammatory Agents; Humans; Models, Biological; Multiple Sclerosis; Myelin Sheath; Nerve Regeneration; Nerve Tissue Proteins; Nervous System Physiological Phenomena; Signal Transduction
PubMed: 20404842
DOI: 10.1038/nrneurol.2010.37 -
Current Opinion in Pharmacology Aug 2022Astrocytes are a group of glial cells that exhibit great morphological, transcriptional and functional diversity both in the resting brain and in response to injury. In... (Review)
Review
Astrocytes are a group of glial cells that exhibit great morphological, transcriptional and functional diversity both in the resting brain and in response to injury. In recent years, astrocytes have attracted increasing interest as therapeutic targets for demyelinating diseases. Following a demyelinating insult, astrocytes can adopt a wide spectrum of reactive states, which can exacerbate damage, but may also facilitate oligodendrocyte progenitor cell differentiation and myelin regeneration. In this review, we provide an overview of recent literature on astrocyte-oligodendrocyte interactions in the context of demyelinating diseases. We highlight novel key roles for astrocytes both during demyelination and remyelination with a focus on potential therapeutic strategies to favor a pro-regenerative astrocyte response in (progressive) multiple sclerosis.
Topics: Astrocytes; Demyelinating Diseases; Humans; Myelin Sheath; Oligodendroglia; Remyelination
PubMed: 35809402
DOI: 10.1016/j.coph.2022.102261 -
Neurologia Oct 2018Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic... (Review)
Review
INTRODUCTION
Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for GFAP have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood.
DEVELOPMENT
The most widespread hypothesis is that AxD develops when a gain of function mutation causes an increase in GFAP. However, this mechanism does not explain myelin loss, given that experimental models in which GFAP expression is normal or mutated do not exhibit myelin disorders. This review analyses other possibilities that may explain this alteration, such as epigenetic or inflammatory alterations, presence of NG2 (+) - GFAP (+) cells, or post-translational modifications in GFAP that are unrelated to increased expression.
CONCLUSIONS
The different hypotheses analysed here may explain the myelin alteration affecting these patients, and multiple mechanisms may coexist. These theories raise the possibility of designing therapies based on these mechanisms.
Topics: Alexander Disease; Animals; Glial Fibrillary Acidic Protein; Humans; Myelin Sheath
PubMed: 28342553
DOI: 10.1016/j.nrl.2017.01.019 -
Cellular and Molecular Life Sciences :... Apr 2014Rapid nerve conduction requires the coating of axons by a tightly packed multilayered myelin membrane. In the central nervous system, myelin is formed from cellular... (Review)
Review
Rapid nerve conduction requires the coating of axons by a tightly packed multilayered myelin membrane. In the central nervous system, myelin is formed from cellular processes that extend from oligodendrocytes and wrap in a spiral fashion around an axon, resulting in the close apposition of adjacent myelin membrane bilayers. In this review, we discuss the physical principles underlying the zippering of the plasma membrane of oligodendrocytes at the cytoplasmic and extracellular leaflet. We propose that the interaction of the myelin basic protein with the cytoplasmic leaflet of the myelin bilayer triggers its polymerization into a fibrous network that drives membrane zippering and protein extrusion. In contrast, the adhesion of the extracellular surfaces of myelin requires the down-regulation of repulsive components of the glycocalyx, in order to uncover weak and unspecific attractive forces that bring the extracellular surfaces into close contact. Unveiling the mechanisms of myelin membrane assembly at the cytoplasmic and extracelluar sites may help to understand how the myelin bilayers are disrupted and destabilized in the different demyelinating diseases.
Topics: Amino Acid Sequence; Cell Membrane; Demyelinating Diseases; Models, Biological; Molecular Sequence Data; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Oligodendroglia; Sequence Alignment
PubMed: 24165921
DOI: 10.1007/s00018-013-1492-0