The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis

Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. Currently approved disease-modifying treatment modalities are immunomodulatory or immunosuppressive. While the applied drugs reduce the frequency and severity of the attacks, their efficacy to regenerate myelin membranes and to halt disease progression is limited. To achieve such therapeutic aims, understanding biological mechanisms of remyelination and identifying factors that interfere with remyelination in MS can give respective directions. Such a perspective is given by the emerging functional profile of galectins. They form a family of tissue lectins, which are potent effectors in processes as diverse as adhesion, apoptosis, immune mediator release or migration. This review focuses on endogenous and exogenous roles of galectins in glial cells such as oligodendrocytes, astrocytes and microglia in the context of de- and (re)myelination and its dysregulation in MS. Evidence is arising for a cooperation among family members so that timed expression and/or secretion of galectins-1, -3 and -4 result in modifying developmental myelination, (neuro)inflammatory processes, de- and remyelination. Dissecting the mechanisms that underlie the distinct activities of galectins and identifying galectins as target or tool to modulate remyelination have the potential to contribute to the development of novel therapeutic strategies for MS.

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New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1973834 ◽

2016 ◽

Vol 2016 ◽

pp. 1-18 ◽

Cited By ~ 44

Author(s):

Bożena Adamczyk ◽

Monika Adamczyk-Sowa

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Chronic Phase ◽

Current Treatment ◽

New Drugs ◽

Inflammatory Processes ◽

The Central Nervous System ◽

The Brain ◽

Methods Of Treatment

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory. The present paper is a review of the current literature about the role of OS in MS and it focuses on all major aspects. The article explains the mechanisms of OS, reports unique biomarkers with regard to their clinical significance, and presents a poorly understood relationship between OS and neurodegeneration. It also provides novel methods of treatment, including the use of antioxidants and the role of antioxidants in neuroprotection. Furthermore, adding new drugs in the treatment of relapse may be useful. The article considers the significance of OS in the current treatment of MS patients.

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Nutrientes y alimentos en la esclerosis múltiple

Archivos Latinoamericanos de Nutrición ◽

10.37527/2020.70.1.007 ◽

2020 ◽

Vol 70 (1) ◽

pp. 60-74

Author(s):

Virginia Sedeño Monge ◽

Eduardo A Fabre Palacios ◽

Cristina López García ◽

María de L Meza Jiménez

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Scientific Evidence ◽

Short Chain Fatty Acids ◽

Vitamina D ◽

Esclerosis Múltiple ◽

Increased Risk ◽

Inflammatory Processes ◽

The Central Nervous System

La alimentación influye en la mejora de la sintomatología de cualquier enfermedad, incluida la esclerosis múltiple (EM),la cual, se caracteriza por un proceso inflamatorio crónico, autoinmune del sistema nervioso central generando situaciones como inflamación, alteraciones; digestivas y mentales, discapacidad, y fatiga. El propósito de la presente revisión fue identificar la evidencia científica sobre los aspectos nutricionales que mejoran la progresión de EM. La metodología consistió en la búsqueda de literatura, en bases de datos electrónicas, referente a nutrición y esclerosis múltiple, principalmente entre los años 2015-2020. Entre los resultados de los aspectos nutricionales que mostraron eficacia en mejorar la progresión de EM, se encuentran el zinc, vitamina D, fibra, probióticos, aceite de pescado y de oliva, cacao, cúrcuma, y salmón. Existen evidencias del papel inmunomodulador del Zn y de la vitamina D en la inhibición de la producción de citocinas proinflamatorias. Niveles bajos de ambos componentes se asocian con mayor riesgo de padecer EM. Otros componentes de interés nutricional son la fibra y probióticos; producen ácidos grasos de cadena corta, con propiedades antiinflamatorias. La primera se conoce por su papel en la motilidad gastrointestinal y los segundos por su acción celular y molecular en procesos inflamatorios, y modulación del microbioma, por mencionar algunos. Los aspectos nutricionales antes mencionados pueden contribuir a modular la inflamación y mejorar la fatiga. Finalmente, este documento genera un panorama importante para continuar con la investigación referente a la influencia de la alimentación en pacientes con EM. Diet influences the improvement of the symptoms of any disease, including multiple sclerosis (MS), which is characterized by a chronic, autoimmune inflammatory process of the central nervous system generating situations such as inflammation, mental and digestive alterations, disability and fatigue. The aim of this review was to identify the scientific evidence on the nutritional aspects that improve the progression of MS. The methodology consisted of searching literature, in electronic databases, referring to nutrition and multiple sclerosis, mainly between the years 2015-2020. The results of the nutritional aspects that showed effectiveness in improving the progression of MS, are zinc, vitamin D, fiber, probiotics, fish oil and olive oil, cocoa, turmeric and salmon. There is evidence of the immunomodulatory role of Zn and vitamin D in inhibiting the production of proinflammatory citokines. Low levels of both components are associated with an increased risk of MS. Other components of nutritional interest are fiber and probiotics; they produce short chain fatty acids, with anti-inflammatory properties. The first is known for its role in gastrointestinal motility and the second one for its cellular and molecular actions in inflammatory processes and the microbiome modulation, to name a few. The nutrition aspects mentioned above, can contribute to modulate inflammation and improve fatigue. Finally, this paper creates an important perspective to continue the investigation concerning the influence of diet in MS patients.

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An association study of two functional promotor polymorphisms in the myeloperoxidase (MPO) gene in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458506075315 ◽

2007 ◽

Vol 13 (6) ◽

pp. 697-700 ◽

Cited By ~ 6

Author(s):

F. Lundmark ◽

H. Salter ◽

J. Hillert

Keyword(s):

Multiple Sclerosis ◽

Complex Disease ◽

Control Material ◽

Gene Encoding ◽

Immunological Responses ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Genetic And Environmental Factors ◽

Large Case

Multiple sclerosis (MS) is a chronic neurological disease affecting the central nervous system (CNS). The disease is characterised by demyelination and axonal loss caused by abnormal immunological responses resulting in accumulating neurological disabilities. MS is considered a complex disease, with both genetic and environmental factors contributing to the pathogenesis. In this study, we have investigated the genetic role of the myeloperoxidase (MPO) gene encoding myeloperoxidase in MS. MPO is an enzyme found in myeloid cells which catalyses the production of hypochlorus acid, a potent microbicidal agent. It also plays an important role in inflammatory processes, where migrating neutrophiles may release active MPO and cause tissue damage. In this study, we investigated two polymorphisms located in the promotor region of the MPO gene, known to influence the expression of MPO, in a large case/control material consisting of 871 Swedish MS patients and 532 Swedish healthy controls. No association was observed with risk of MS. Multiple Sclerosis 2007; 13: 697-700. http://msj.sagepub.com

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Potential Role of Trace Elements (Al, Cu, Zn, and Se) in Multiple Sclerosis Physiopathology

NeuroImmunoModulation ◽

10.1159/000511308 ◽

2020 ◽

Vol 27 (4) ◽

pp. 163-177

Author(s):

Mohammad Sadegh Hesamian ◽

Nahid Eskandari

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Trace Elements ◽

Plasma Cells ◽

Peripheral Tolerance ◽

The Central Nervous System ◽

Living Organisms ◽

Tolerance Breakdown ◽

Peripheral Immune Cells

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body’s functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.

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Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

Biological Research For Nursing ◽

10.1177/10998004211050082 ◽

2021 ◽

pp. 109980042110500

Author(s):

Pamela Newland ◽

Yelyzaveta Basan ◽

Ling Chen ◽

Gregory Wu

Keyword(s):

Multiple Sclerosis ◽

Inflammatory Markers ◽

Pearson Correlation ◽

Correlation Coefficients ◽

The United States ◽

Biological Mechanisms ◽

The Central Nervous System ◽

Brain And Spinal Cord ◽

The Brain

Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system (CNS), afflicts over one per thousand people in the United States. The pathology of MS typically involves lesions in several regions, including the brain and spinal cord. The manifestation of MS is variable and carries great potential to negatively impact quality of life (QOL). Evidence that inflammatory markers are related to depression in MS is accumulating. However, there are barriers in precisely identifying the biological mechanisms underlying depression and inflammation. Analysis of cytokines provides one promising approach for understanding the mechanisms that may contribute to MS symptoms. Methods: In this pilot study, we measured salivary levels of interleukin (IL)-6, IL-1beta (β), and IL-10 in 24 veterans with MS. Descriptive statistics were reported and Pearson correlation coefficients were obtained between cytokines and depression. Results: The anti-inflammatory cytokine IL-10 was significantly negatively associated with depression in veterans with MS (r = −0.47, p = .024). Conclusion: Cytokines may be useful for elucidating biological mechanisms associated with the depression and a measure for nurses caring for veterans with MS.

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Multiple Sclerosis and Obesity: Possible Roles of Adipokines

Mediators of Inflammation ◽

10.1155/2016/4036232 ◽

2016 ◽

Vol 2016 ◽

pp. 1-24 ◽

Cited By ~ 36

Author(s):

José de Jesús Guerrero-García ◽

Lucrecia Carrera-Quintanar ◽

Rocío Ivette López-Roa ◽

Ana Laura Márquez-Aguirre ◽

Argelia Esperanza Rojas-Mayorquín ◽

...

Keyword(s):

Multiple Sclerosis ◽

Early Life ◽

Neural Tissue ◽

Autoimmune Disorder ◽

Susceptibility Factor ◽

Related Risk ◽

Inflammatory State ◽

The Central Nervous System ◽

Ms Pathogenesis

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS.

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GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis

Science Translational Medicine ◽

10.1126/scitranslmed.aat4301 ◽

2018 ◽

Vol 10 (462) ◽

pp. eaat4301 ◽

Cited By ~ 19

Author(s):

Raquel Planas ◽

Radleigh Santos ◽

Paula Tomas-Ojer ◽

Carolina Cruciani ◽

Andreas Lutterotti ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Cell Clone ◽

Autoimmune Response ◽

Guanosine Diphosphate ◽

Immune Mediated ◽

T Cell Clone ◽

Positional Scanning ◽

The Central Nervous System

Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.

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Advances in microglia cellular models: focus on extracellular vesicle production

Biochemical Society Transactions ◽

10.1042/bst20210203 ◽

2021 ◽

Author(s):

Lorenzo Ceccarelli ◽

Laura Marchetti ◽

Chiara Giacomelli ◽

Claudia Martini

Keyword(s):

Cell Communication ◽

Extracellular Vesicle ◽

Cellular Models ◽

Advantages And Disadvantages ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Harmful Effects ◽

Brain Homeostasis

Microglia are the major component of the innate immune system in the central nervous system. They promote the maintenance of brain homeostasis as well as support inflammatory processes that are often related to pathological conditions such as neurodegenerative diseases. Depending on the stimulus received, microglia cells dynamically change their phenotype releasing specific soluble factors and largely modify the cargo of their secreted extracellular vesicles (EVs). Despite the mechanisms at the basis of microglia actions have not been completely clarified, the recognized functions exerted by their EVs in patho-physiological conditions represent the proof of the crucial role of these organelles in tuning cell-to-cell communication, promoting either protective or harmful effects. Consistently, in vitro cell models to better elucidate microglia EV production and mechanisms of their release have been increased in the last years. In this review, the main microglial cellular models that have been developed and validated will be described and discussed, with particular focus on those used to produce and derive EVs. The advantages and disadvantages of their use will be evidenced too. Finally, given the wide interest in applying EVs in diagnosis and therapy too, the heterogeneity of available models for producing microglia EVs is here underlined, to prompt a cross-check or comparison among them.

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Vitamin D Immunomodulatory Potential in Multiple Sclerosis

Folia Medica ◽

10.2478/folmed-2013-0011 ◽

2013 ◽

Vol 55 (2) ◽

pp. 5-9 ◽

Cited By ~ 4

Author(s):

Georgi S. Slavov ◽

Anastasiya G. Trenova ◽

Mariya G. Manova ◽

Ivanka I. Kostadinova ◽

Tonka V. Vasileva ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Clinical Studies ◽

Short Interval ◽

Unknown Etiology ◽

Vitamin D Metabolism ◽

Social Burden ◽

25 Hydroxy Vitamin D ◽

The Central Nervous System ◽

Immunomodulatory Potential

ABSTRACT Multiple sclerosis (MS) is an autoimmune disease of unknown etiology whose treatment is of limited efficiency and therefore has a high social burden. As it has been suggested that myelin destruction model, the clinical manifestation and the potential of therapeutic response in MS are correlated, it is quite justifiable that we study various factors (genetic, hormonal, environmental) that take part in the autoimmune process in order to improve the control over the disrupted immune regulation. Results from epidemiological and clinical studies clearly suggest that changes in vitamin D serum concentrations are correlated with the magnitude of the risk of developing MS, the phases of relapse and remittance and with gender differences in vitamin D metabolism. Experimental and clinical studies also have established that 25-hydroxy vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) exert an immunomodulatory effect in the central nervous system and peripheral organs of the immune system. The standard reference range of vitamin D concentration in serum is 50-80 nmol/l - it provides normal calcium metabolism. Issues that are discussed include the vitamin D serum concentration needed to suppress the aberrant immune response in MS patients; a subgroup of MS patients suitable for vitamin D treatment, the vitamin D being applied in optimally effective and safe dosage. MS prevalence rate in Bulgaria has increased two-fold in 17 years but this is a rather short interval to be able to assume that the gene pool of the population changes. Thus further studies on possible interactions between different environmental factors and these factors’ role in the disease pathogenesis are justified and necessary.

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