scholarly journals Insights into abnormal sphingolipid metabolism in multiple sclerosis: targeting ceramide biosynthesis as a unique therapeutic strategy

2018 ◽  
Vol 4 ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Strategy ◽  
Sphingolipid Metabolism

scholarly journals PADI2-mediated citrullination is required for efficient oligodendrocyte differentiation and myelination

2018 ◽  
Author(s):  
Ana Mendanha Falcão ◽  
Mandy Meijer ◽  
Antonella Scaglione ◽  
Puneet Rinwa ◽  
Eneritz Agirre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Therapeutic Strategy ◽  
Chromatin Accessibility ◽  
Motor Dysfunction ◽  
Peptidylarginine Deiminase ◽  
Oligodendrocyte Differentiation ◽  
Associated Proteins ◽  
Arginine Residues ◽  
Related Proteins

Citrullination, the deimination of arginine residues into citrulline, has been implicated in the aetiology of several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver of pathology, through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutic strategy for MS. Here, in contrast, we show citrullination by peptidylarginine deiminase 2 (PADI2) is required for normal oligodendrocyte differentiation, myelination and motor function. We identify several targets for PADI2, including myelin-related proteins and chromatin-associated proteins, implicating PADI2 in epigenetic regulation. Accordingly, we observe that PADI2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of oligodendrocyte differentiation genes. Moreover, mice lacking PADI2, display motor dysfunction and decreased number of myelinated axons in the corpus callosum. We conclude that citrullination is required for oligodendrocyte lineage progression and myelination and suggest its targeted activation in the oligodendrocyte lineage might be beneficial in the context of remyelination.

Mitochondria-targeted Antioxidants as a Prospective Therapeutic Strategy for Multiple Sclerosis

2017 ◽  
Vol 24 (19) ◽  
Author(s):  
Elena Fetisova ◽  
Boris Chernyak ◽  
Galina Korshunova ◽  
Maria Muntyan ◽  
Vladimir Skulachev
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Strategy

scholarly journals Small Molecule Inhibitor of Antigen Binding and Presentation by HLA-DR2b as a Therapeutic Strategy for the Treatment of Multiple Sclerosis

2013 ◽  
Vol 191 (10) ◽  
pp. 5074-5084 ◽  
Author(s):  
Niannian Ji ◽  
Animesh Somanaboeina ◽  
Aakanksha Dixit ◽  
Kazuyuki Kawamura ◽  
Neil J. Hayward ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Small Molecule ◽  
Therapeutic Strategy ◽  
Small Molecule Inhibitor ◽  
Antigen Binding ◽  
Molecule Inhibitor

scholarly journals Transplantation Options for Therapeutic Central Nervous System Remyelination

2000 ◽  
Vol 9 (2) ◽  
pp. 289-294 ◽  
Author(s):  
William F. Blakemore ◽  
Robin J. M. Franklin
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Strategy ◽  
Functional Testing ◽  
Spinal Cord Trauma ◽  
Experimental Animals ◽  
Functional Deficit ◽  
Lineage Differentiation ◽  
Degree Of Certainty ◽  
Embryonic Cns

Persistent demyelination, in addition to being the major pathology of multiple sclerosis and the leucodystrophies, is also a feature of spinal cord trauma where there is evidence that it contributes to the functional deficit. In experimental animals it is possible to remyelinate demyelinated CNS axons by transplanting cultures containing central or peripheral myelinogenic cells. Using functional testing we have been able to show that transplant-mediated remyelination results in restoration of function lost as a consequence of demyelination. Glial cell transplantation may therefore provide a therapeutic strategy for remyelinating areas of chronic demyelination. This article reviews issues that have to be addressed before glial transplantation can be undertaken in humans. These include: what cells to use, where would the cells come from, and can we predict how much remyelination will be achieved? It concludes that the most promising approach will be to use neural multipotential stem cells isolated from embryonic CNS, expanded in vitro as neurospheres and then committed to oligodendrocyte lineage differentiation prior to implantation. However, even with such preparations, which have considerable myelinating potential, the extent of remyelination that will be achieved cannot currently be predicted with any degree of certainty.

Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development

2003 ◽  
Vol 9 (6) ◽  
pp. 574-578 ◽  
Author(s):  
Akio Suzumura ◽  
Atsushi Ito ◽  
Tetsuya Mizuno
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Strategy ◽  
Phosphodiesterase Inhibitors ◽  
T Helper ◽  
T Helper 1 ◽  
Chain Reaction ◽  
The Central Nervous System ◽  
Antigen Presenting

The effects of phosphodiesterase inhibitors (PDEIs) on interleukin (IL)-12 production by microglia, antigen-presenting cells in the central nervous system (C NS), were examined to learn how they affect T cell differentiatio n in the C NS. PDEIs significantly suppressed the microglial IL-12 production, as determined by reverse transcriptase-po lymerase chain reaction for IL-12 p35 and p40 mRNA expression and by an ELISA specific for IL-12 functional hetero dimer, p70. In addition, the PDEI ibudilast also suppressed interferon-g, but not IL-4 or IL-10, production by myelin oligodendro cyte glycoprotein (MO G)-specific T cells reactivated with MO G in the presence of microglia. Thus, PDEIs may also suppress differentiatio n of T helper 1 (Th1) in the C NS. PDEIs can be of use for future therapeutic strategy to treat Th1-mediated diseases, such as multiple sclerosis.

scholarly journals Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Marjana Brkic ◽  
Sriram Balusu ◽  
Claude Libert ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Matrix Metalloproteinases ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Pathological Conditions ◽  
Progressive Loss ◽  
Neuro Inflammation ◽  
Potential Use ◽  
Lateral Sclerosis

Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

scholarly journals Stabilization Without Rituximab After Disease Activation in an Alemtuzumab-Treated Patient with Multiple Sclerosis and a Literature Overview

2019 ◽  
Vol 21 (3) ◽  
pp. 125-128
Author(s):  
Chantal Kahovec ◽  
Michael C. Levin
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Therapeutic Strategy ◽  
Vision Loss ◽  
Treated Patient ◽  
Brain Magnetic Resonance Imaging ◽  
Resonance Imaging ◽  
Gadolinium Enhancement ◽  
Cell Counts ◽  
Literature Overview

Abstract There has been an increasing number of reports describing B-cell–associated disease activation in patients with multiple sclerosis after alemtuzumab treatment. Herein, 4.5 months after a first alemtuzumab infusion, a 33-year-old female patient had altered gait and vision loss associated with gadolinium enhancement of the optic nerves and chiasm on brain magnetic resonance imaging. The patient's blood showed normal B-cell counts concurrent with abnormally low T-cell counts. The patient stabilized after receiving steroids and prolonged plasma exchange without the use of rituximab. This case report adds to the growing body of literature of B-cell–associated disease activation after alemtuzumab infusion and provides a therapeutic strategy to stabilize patients when rituximab is not readily available or if contraindications to its use exist.

scholarly journals Understanding the Roles of the Kynurenine Pathway in Multiple Sclerosis Progression

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4294 ◽  
Author(s):  
Chai K. Lim ◽  
Bruce J. Brew ◽  
Gayathri Sundaram ◽  
Gilles J. Guillemin
Keyword(s):  
Multiple Sclerosis ◽  
Nicotinamide Adenine Dinucleotide ◽  
Brain Tumours ◽  
Therapeutic Strategy ◽  
Inflammatory Diseases ◽  
Kynurenine Pathway ◽  
Aids Dementia Complex ◽  
Regulatory Mechanisms ◽  
Aids Dementia ◽  
Lateral Sclerosis

The kynurenine pathway (KP) is a major degradative pathway of tryptophan ultimately leading to the production of nicotinamide adenine dinucleotide (NAD+) and is also one of the major regulatory mechanisms of the immune response. The KP is known to be involved in several neuroinflammatory disorders including Alzheimer's disease, amyotrophic lateral sclerosis, AIDS dementia complex, Parkinson's disease, schizophrenia, Huntington's disease and brain tumours. However, the KP remains a relatively new topic for the field of multiple sclerosis (MS). Over the last 2–3 years, some evidence has progressively emerged suggesting that the KP is likely to be involved in the pathogenesis of autoimmune diseases especially MS. Some KP modulators are already in clinical trials for other inflammatory diseases and would potentially provide a new and important therapeutic strategy for MS patients. This review summarizes the known relationships between the KP and MS.

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