☆ 4.6 Review

Inflammation in multiple sclerosis: consequences for remyelination and disease progression

NATURE REVIEWS NEUROLOGY (2023)

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Article Biochemistry & Molecular Biology

Pharmacological treatment promoting remyelination enhances motor function after internal capsule demyelination in mice

Reiji Yamazaki et al.

Summary: Multiple sclerosis (MS) is characterized by remyelination failure, axonal degeneration, and progressive worsening of motor functions. Animal models of demyelination are commonly used to develop and evaluate therapies for MS. In this study, the focal internal capsule (IC) demyelination mouse model was used to examine the effect of clemastine, an anti-muscarinic drug that promotes remyelination, on motor functions. Clemastine administration improved motor function and increased myelination in the IC lesions, suggesting that the IC demyelination model is useful for evaluating changes in motor functions following pharmacological treatments.

NEUROCHEMISTRY INTERNATIONAL (2023)

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Article Clinical Neurology

Phase 1 Evaluation of Elezanumab (Anti-Repulsive Guidance Molecule A Monoclonal Antibody) in Healthy and Multiple Sclerosis Participants

Hari V. V. Kalluri et al.

Summary: This study focuses on the safety, tolerability, pharmacokinetics, and immunogenicity of elezanumab in healthy individuals and multiple sclerosis patients. The results demonstrate that elezanumab does not cause adverse events and has dose-dependent increases in cerebrospinal fluid concentrations.

ANNALS OF NEUROLOGY (2023)

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Article Clinical Neurology

Periventricular remyelination failure in multiple sclerosis: a substrate for neurodegeneration

Matteo Tonietto et al.

Summary: This study explores the regional distribution of myelin repair in multiple sclerosis and its relationship with neurodegeneration. The findings show that periventricular white matter lesions in multiple sclerosis patients exhibit selective failure of remyelination, which is associated with choroid plexus enlargement and grey matter atrophy. The study highlights the importance of myelin repair in protecting against cortical damage in multiple sclerosis.

BRAIN (2023)

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Article Clinical Neurology

Human Oligodendrocyte Myelination Potential; Relation to Age and Differentiation

Julia Xiao Xuan Luo et al.

Summary: The study investigates the effects of age and differentiation on the myelination potential of human OL lineage cells. The results show that pediatric progenitor and mature cells have a stronger capacity for ensheathing nanofibers compared to their adult counterparts. Additionally, certain gene expressions are higher in pediatric cells. These findings suggest potential targets for enhancing remyelination therapies.

ANNALS OF NEUROLOGY (2022)

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Article Biochemistry & Molecular Biology

DNA methylation changes in glial cells of the normal-appearing white matter in Multiple Sclerosis patients

Lara Kular et al.

Summary: This study examines DNA methylation in glial cells to uncover molecular changes underlying Multiple Sclerosis (MS) neuropathology. The researchers identified significant differential methylation positions between MS patients and controls, and found alterations in processes related to cellular motility, metabolic processes, neuroinflammation, and signaling. Genes affected by the methylation changes showed transcriptional differences in the brains of MS patients. The findings suggest a multicellular reaction in response to inflammation in the absence of lesional insult.

EPIGENETICS (2022)

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Article Neurosciences

New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination

Sarah A. Neely et al.

Summary: Through research on zebrafish, it was found that surviving oligodendrocytes are less efficient in generating new myelin sheaths and frequently misdirect the myelin to neuronal cell bodies, which is similar to the pathology seen in multiple sclerosis (MS). Conversely, oligodendrocytes generated after demyelination produce abundant and correctly targeted myelin sheaths, suggesting that they may also have a better regenerative potential in MS.

NATURE NEUROSCIENCE (2022)

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Article Multidisciplinary Sciences

MACSima imaging cyclic staining (MICS) technology reveals combinatorial target pairs for CAR T cell treatment of solid tumors

Ali Kinkhabwala et al.

Summary: MICS technology is a new high-content microscopy technique that allows immunofluorescent imaging of hundreds of protein targets at subcellular resolution. It can identify potential targets for immune therapy and has wide applicability in personalized medicine.

SCIENTIFIC REPORTS (2022)

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Review Clinical Neurology

Remyelination trial failures: Repercussions of ignoring neurorehabilitation and exercise in repair

Michelle Ploughman et al.

Summary: Several putative neurorestorative therapies in multiple sclerosis have recently failed, potentially due to the absence of exercise and participants without the capacity for repair. The authors argue for mapping the biological mechanisms of recovery, identifying the critical window for remyelination/repair, and selecting suitable subjects for interventions. They also propose testing combinations of pro-repair interventions, such as exercise, Nrf2 inducers, and neurostimulation.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2022)

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Article Neurosciences

Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling

Jamie M. Walker et al.

Summary: Resilient individuals exhibit protein expression patterns suggestive of an environment with less energetic and oxidative stress, resulting in the maintenance of neuronal and synaptic integrity.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2022)

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Article Neurosciences

Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter

Anneke Miedema et al.

Summary: In this study, the early changes in multiple sclerosis (MS) brain tissue were characterized through transcriptomic analysis. The findings revealed an increased stress response in brain macrophages in the normal appearing white matter (NAWM) of MS patients, and specific microglia and macrophage subsets were identified at different stages of demyelinating lesions.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2022)

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Article Biochemistry & Molecular Biology

Regulatory Cells in Multiple Sclerosis: From Blood to Brain

Leticia Calahorra et al.

Summary: Multiple sclerosis (MS) is a chronic, autoimmune, and neurodegenerative disease of the central nervous system (CNS) characterized by the demyelination of nerve fibers. While T cells were traditionally thought to be the key players in MS pathogenesis, recent research has highlighted the significant roles of B lymphocytes and innate immune cells. Protective regulatory cells, such as myeloid-derived suppressor cells and regulatory T and B cells, are increasingly recognized for their potential in therapy development for MS.

BIOMEDICINES (2022)

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Article Clinical Neurology

Diverse injury responses of human oligodendrocyte to mediators implicated in multiple sclerosis

Florian Pernin et al.

Summary: The early lesions of multiple sclerosis involve the degeneration of myelinating processes of oligodendrocytes, while the cell bodies of these cells are relatively preserved. As the disease progresses, there is loss of oligodendrocytes. The injury mediators that contribute to this process include metabolic stress, pro-inflammatory mediators, and excitotoxins. It is important to understand the specific effects of these mediators on human oligodendrocytes in order to develop effective neuroprotective therapies for multiple sclerosis.

BRAIN (2022)

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Article Pharmacology & Pharmacy

Innate and adaptive immune mechanisms regulating central nervous system remyelination

Richard Creswell et al.

Summary: Neuroinflammation is a characteristic of many neurodegenerative diseases and plays a crucial role in the regeneration of myelin after damage. Both innate and adaptive immune mechanisms are important for successful remyelination, but the specific role of the adaptive immune system is still unclear. Harnessing the beneficial aspects of neuroinflammation could lead to future therapies for regenerating the central nervous system.

CURRENT OPINION IN PHARMACOLOGY (2022)

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Article Clinical Neurology

Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study

Hans-Peter Hartung et al.

Summary: The study did not meet its primary endpoint, but at 48 weeks participants treated with 18 mg/kg temelimab had fewer new T1-hypointense lesions. They also showed consistent, although statistically non-significant, reductions in brain atrophy and magnetization transfer ratio decrease compared to the placebo/comparator group. These trends were sustained over 96 weeks with no safety issues emerging.

MULTIPLE SCLEROSIS JOURNAL (2022)

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Article Clinical Neurology

Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial

Douglas L. Arnold et al.

Summary: The study found that siponimod treatment can slow down brain tissue damage and myelination process in patients with multiple sclerosis. This provides important information for better understanding of brain tissue integrity in patients with multiple sclerosis.

MULTIPLE SCLEROSIS JOURNAL (2022)

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Article Multidisciplinary Sciences

Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination

Samira Ghorbani et al.

Summary: Ghorbani and colleagues have found that versican-V1 acts as an inhibitor of oligodendrocyte regeneration by directly inhibiting oligodendrocytes and promoting the production of Th17 cells. In experimental models of multiple sclerosis, versican-V1 is selectively upregulated among other chondroitin sulfate proteoglycans (CSPGs). The study suggests that reducing CSPG levels could be a potential therapeutic approach for promoting repair and modulating the immune response in multiple sclerosis.

NATURE COMMUNICATIONS (2022)

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Article Clinical Neurology

Remyelination in humans due to a retinoid-X receptor agonist is age-dependent

Christopher E. McMurran et al.

Summary: Remyelination efficiency decreases with age, particularly in patients with multiple sclerosis. Bexarotene, a retinoid-X receptor agonist, only shortens the visual evoked potential latency in patients under 42 years old and increases the magnetization transfer ratio of deep gray matter lesions in those under 43 years old.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2022)

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Article Clinical Neurology

Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models

Michael Dietrich et al.

Summary: This study confirms the immunomodulatory effects of Siponimod and suggests additional regenerative and promyelinating effects, which follow the dynamics of a bell-shaped curve with high concentrations being less efficient than low concentrations.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2022)

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Review Clinical Neurology

Contribution of B cells to cortical damage in multiple sclerosis

Pavan Bhargava et al.

Summary: This article reviews the role of B cells in mediating cortical demyelination and neuronal damage in multiple sclerosis. The authors summarize the evidence linking B cells to cortical injury, potential mechanisms by which B cells may mediate oligodendrocyte and neuronal death, and treatment strategies that could be used to target pathogenic B cells.

BRAIN (2022)

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Review Clinical Neurology

New drugs for multiple sclerosis: new treatment algorithms

Bruce A. C. Cree et al.

Summary: This article discusses recent changes in the treatment algorithm for multiple sclerosis (MS) and presents therapies currently being tested in clinical trials. Recent findings suggest that high efficacy disease modifying therapies are best when used in the early inflammatory phase of MS. Bruton's tyrosine kinase has emerged as an important therapeutic target for both relapsing and progressive forms of the disease. While multiple therapies targeting remyelination have not provided conclusive evidence of broad therapeutic benefit, more targeted approaches offer hope for achieving myelin repair and specific clinical improvements. Strategies targeting chronic Epstein-Barr virus infection and dysbiosis of the gut microbiome are the first to link microbial risk factors for MS and therapeutic interventions. The diverse array of treatments currently under investigation holds promise for the development of better and more effective therapies for MS.

CURRENT OPINION IN NEUROLOGY (2022)

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Article Pharmacology & Pharmacy

Recent insights into astrocytes as therapeutic targets for demyelinating diseases

Rianne Petra Gorter et al.

Summary: Astrocytes play vital roles in demyelinating diseases, promoting remyelination. This review summarizes recent research on astrocyte-oligodendrocyte interactions and discusses potential therapeutic strategies to enhance regenerative astrocyte responses in (progressive) multiple sclerosis.

CURRENT OPINION IN PHARMACOLOGY (2022)

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Article Neurosciences

Regional and age-related diversity of human mature oligodendrocytes

Moein Yaqubi et al.

Summary: Morphological and molecular studies have shown that there is heterogeneity within the oligodendrocyte population in the human central nervous system. Through single-cell RNA sequencing, this study identified transcriptionally distinct subpopulations of mature oligodendrocytes in different regions and at different ages. The findings suggest that the heterogeneity of oligodendrocyte populations may be influenced by developmental and environmental factors.

GLIA (2022)

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Article Clinical Neurology

Clinically relevant profiles of myelin content changes in patients with multiple sclerosis: A multimodal and multicompartment imaging study

Andrea Lazzarotto et al.

Summary: By combining MTI and PET, we can study the myelin content changes in cortical and white matter lesions in patients with multiple sclerosis. This has significant implications for clinical assessment and treatment.

MULTIPLE SCLEROSIS JOURNAL (2022)

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Article Neurosciences

Identification of early neurodegenerative pathways in progressive multiple sclerosis

Max Kaufmann et al.

Summary: This study identified multicellular mechanisms of progressive multiple sclerosis (MS) pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration by using spatial transcriptomics and proteomics. Defunct trophic and anti-inflammatory intercellular communications were discovered within areas of early neuronal decline in MS patients. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with in vivo knockdown and central nervous system (CNS) disease models. This study provides a new framework for drug development strategies and uncovers new therapeutic opportunities to slow disease.

NATURE NEUROSCIENCE (2022)

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Review Clinical Neurology

Emerging therapies to target CNS pathophysiology in multiple sclerosis

Jiwon Oh et al.

Summary: In this Review, the authors provide an overview of emerging therapies for multiple sclerosis that have the potential to limit disease progression and promote tissue repair. The treatment of relapsing-remitting MS can still be improved, and there is a need to target progressive disease mechanisms and repair central nervous system (CNS) injury. The authors focus on therapies that target processes within the CNS, such as inflammation, degenerative mechanisms, neuroprotection, and oligodendrocyte precursor cell differentiation, remyelination, and axonal regeneration.

NATURE REVIEWS NEUROLOGY (2022)

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Article Plant Sciences

Ginsenoside Rg1 promotes remyelination and functional recovery in demyelinating disease by enhancing oligodendrocyte precursor cells-mediated myelin repair

Li Liu et al.

Summary: This study found that ginsenoside Rg1 (Rg1) promotes differentiation of oligodendrocyte precursor cells (OPCs) and myelin regeneration, showing promising therapeutic significance for functional recovery in neurodegenerative diseases such as multiple sclerosis.

PHYTOMEDICINE (2022)

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Article Clinical Neurology

Cross-regional homeostatic and reactive glial signatures in multiple sclerosis

Tim Trobisch et al.

Summary: In patients with multiple sclerosis (MS), it was found that the transcriptomic characteristics of astrocytes overlap across different regions, and different reactive glial cell types may exacerbate or ameliorate pathology.

ACTA NEUROPATHOLOGICA (2022)

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Review Clinical Neurology

What Have Failed, Interrupted, and Withdrawn Antibody Therapies in Multiple Sclerosis Taught Us?

Julia Kraemer et al.

Summary: The review highlights the importance of safety evaluation, the role of memory B cells in immunopathogenesis, and the relationship between pathophysiology and treatment outcomes when utilizing monoclonal antibodies for the treatment of multiple sclerosis. Understanding these aspects is crucial for optimizing future trial designs and improving therapeutic efficacy.

NEUROTHERAPEUTICS (2022)

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Review Immunology

Immune ageing at single-cell resolution

Denis A. Mogilenko et al.

Summary: Studying ageing at the single-cell level has provided a greater understanding of the heterogeneity and dynamic nature of immune cell ageing, as well as the impact of age-associated tissue remodelling on the immune system. The widespread application of single-cell techniques has enabled substantial progress in our understanding of the ageing immune system.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Cell Biology

Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin

Robin J. M. Franklina et al.

Summary: The biology of CNS remyelination has attracted interest due to its potential for regenerative therapies. Recent studies have identified two modes of remyelination, raising questions for future research.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2021)

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Article Neurosciences

Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis

Stefan A. Berghoff et al.

Summary: The study reveals that sterol synthesis in microglia/macrophages is crucial for resolving inflammation and inducing remyelination in the repair of demyelinated lesions in multiple sclerosis (MS), with desmosterol activating LXR signaling as a key mechanism.

NATURE NEUROSCIENCE (2021)

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Article Clinical Neurology

Effects of Ibudilast on MRI Measures in the Phase 2 SPRINT-MS Study

Robert T. Naismith et al.

Summary: The study aimed to assess the effects of ibudilast on brain volume and new lesions in progressive forms of MS. Results showed that ibudilast reduced gray matter atrophy but did not reduce new or enlarging T2 lesions or new T1 lesions.

NEUROLOGY (2021)

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Article Immunology

Citrullinated myelin induces microglial TNFα and inhibits endogenous repair in the cuprizone model of demyelination

Miranda M. Standiford et al.

Summary: This study revealed that citrullinated myelin induces a unique microglial response with increased production of tumor necrosis factor alpha (TNF alpha). Injection of citrullinated myelin inhibits spontaneous remyelination significantly, while neutralization of TNF alpha restores remyelination to normal levels.

JOURNAL OF NEUROINFLAMMATION (2021)

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Article Clinical Neurology

Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study

Wolf A. Lagreze et al.

Summary: The study showed that erythropoietin as an adjunct to corticosteroids did not provide neuroprotection in the visual pathways after optic neuritis. Future research could focus on modified erythropoietin administration, assess its efficacy independent of corticosteroids, and investigate whether it affects the conversion of optic neuritis to multiple sclerosis.

LANCET NEUROLOGY (2021)

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Article Immunology

Highly multiplexed tissue imaging using repeated oligonucleotide exchange reaction

Julia Kennedy-Darling et al.

Summary: Researches have developed a novel multiplexed imaging method by simplifying the process and creating a panel of antibodies, enabling simultaneous staining of multiple antibodies in human tissues. This method reveals cell types in tissue structures, providing a way to explore tissue homeostasis and disease mechanisms.

EUROPEAN JOURNAL OF IMMUNOLOGY (2021)

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Article Multidisciplinary Sciences

AIM2 in regulatory T cells restrains autoimmune diseases

Wei-Chun Chou et al.

Summary: The inflammasome activates inflammatory responses in myeloid cells, while the AIM2 receptor plays an independent role in regulating T-reg cells. AIM2 inhibits AKT phosphorylation, alters immune metabolism to enhance T-reg cell stability, and reduces autoimmune responses independent of the inflammasome.

NATURE (2021)

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Article Genetics & Heredity

Deep characterization of paired chromatin and transcriptomes in four immune cell types from multiple sclerosis patients

Sunjay Jude Fernandes et al.

Summary: This study explores the primary role of CD4(+) and CD19(+) cells in multiple sclerosis (MS), identifying CCDC114 and SERTAD1 as two dysregulated genes through multilayer analysis. These findings offer new insights into understanding MS and its genetic, epigenetic, and transcriptional mechanisms.

EPIGENOMICS (2021)

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Review Cell Biology

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Greg J. Duncan et al.

Summary: Oligodendrocytes play a crucial role in myelinating axons, and disruptions in this relationship can lead to axonal dysfunction and neurodegeneration. Understanding the mechanisms behind demyelination and loss of oligodendrocytes is important in developing potential therapeutic strategies for disorders where oligodendrocyte support of axons is compromised.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Article Neurosciences

CHPG enhances BDNF and myelination in cuprizone-treated mice through astrocytic metabotropic glutamate receptor 5

Kyle S. Saitta et al.

Summary: The study suggests that the mGluR agonist CHPG may be a potential therapeutic strategy for demyelinating diseases by enhancing the release of BDNF from astrocytes.

GLIA (2021)

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Article Multidisciplinary Sciences

Barcoded viral tracing of single-cell interactions in central nervous system inflammation

Iain C. Clark et al.

Summary: The study identified microglia-astrocyte interactions and candidate therapeutic targets using RABID-seq, providing new insights into CNS pathology.

SCIENCE (2021)

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Review Pharmacology & Pharmacy

Failed, Interrupted, or Inconclusive Trials on Neuroprotective and Neuroregenerative Treatment Strategies in Multiple Sclerosis: Update 2015-2020

Niklas Huntemann et al.

Summary: Numerous drugs have been approved for treating multiple sclerosis in recent years, mainly focusing on immunomodulatory or immunosuppressive strategies rather than remyelination and neuroprotection. Neuroregenerative agents have shown potential in pre-clinical research and clinical trials, providing valuable insights into MS pathophysiology. Learning from failed trials can aid in translating pre-clinical findings into clinical applications for improved treatments.

DRUGS (2021)

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Article Immunology

TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination

Garyfallia Gouna et al.

Summary: Microglia play a key role in promoting myelin repair after demyelinating injury, with cholesterol esterification being essential for myelin debris clearance and lipid droplet generation. TREM2 is crucial for adapting to excess cholesterol exposure and regulating lipid droplet formation, ultimately impacting the innate immune response and remyelination.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Immunology

Anti-CD20 treatment effectively attenuates cortical pathology in a rat model of widespread cortical demyelination

Michaela T. Haindl et al.

Summary: In a rat model, B-cell depleting anti-CD20 therapy showed significant reductions in cortical demyelination, microglial activation, astrocytic reaction, and apoptotic cell loss, while also increasing neuronal preservation. These findings suggest a beneficial impact of anti-CD20 therapy on progressive forms of MS and may lead to improved therapeutic options in the future.

JOURNAL OF NEUROINFLAMMATION (2021)

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Article Clinical Neurology

Multiple Sclerosis: Microglia, Monocytes, and Macrophage-Mediated Demyelination

John W. Prineas et al.

Summary: The study showed that microglia and monocytes play important roles in myelin destruction in early multiple sclerosis patients, with newly identified cell types and a new gray matter lesion observed in MS.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2021)

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Article Clinical Neurology

Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One) a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study

J. William L. Brown et al.

Summary: This study aimed to evaluate the safety and efficacy of non-selective retinoid X receptor agonist bexarotene in promoting remyelination in patients with multiple sclerosis. The results showed that the bexarotene treatment group had more adverse events and poor efficacy outcome, therefore not recommended for the treatment of multiple sclerosis.

LANCET NEUROLOGY (2021)

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Article Multidisciplinary Sciences

A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis

Martina Absinta et al.

Summary: Through MRI-guided single-nucleus RNA sequencing, a diversity of glial and immune cells at the edge of demyelinated white matter lesions in multiple sclerosis (MS) have been identified, along with the definition of inflamed glial cell phenotypes in MS. The overlap of the transcriptional profile of microglia inflamed in MS with that in other neurodegenerative diseases suggests common mechanisms between primary and secondary neurodegeneration that could benefit from similar therapeutic approaches. The critical role of complement component 1q (C1q) in the activation of microglia inflamed in MS has been identified and potential therapeutic avenues, such as C1q inhibition, have been suggested for addressing chronic white matter inflammation.

NATURE (2021)

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Article Multidisciplinary Sciences

Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation

Catherine Larochelle et al.

Summary: Th17 cells play a significant role in multiple sclerosis, causing glutamate release and changes in myelination when in contact with oligodendrocytes. Blocking CD29 can protect oligodendrocytes from Th17-mediated injury, offering new therapeutic potential for multiple sclerosis.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Neurosciences

IL-17 Inhibits Oligodendrocyte Progenitor Cell Proliferation and Differentiation by Increasing K+ Channel Kv1.3

Han Liu et al.

Summary: IL-17 induces myelin damage through Kv1.3 activation, inhibiting proliferation and differentiation of Ol, impairing remyelination. Blocking Kv1.3 could be a potential therapeutic strategy for inflammatory CNS diseases by protecting OPC proliferation and differentiation.

FRONTIERS IN CELLULAR NEUROSCIENCE (2021)

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Review Neurosciences

Connecting Neuroinflammation and Neurodegeneration in Multiple Sclerosis: Are Oligodendrocyte Precursor Cells a Nexus of Disease?

Morgan W. Psenicka et al.

Summary: Neurodegenerative diseases often involve inflammation, and multiple sclerosis (MS) is a complex interplay between inflammation and neurodegeneration. Oligodendrocyte precursor cells (OPCs) play an active role in promoting neuroinflammation and neurodegeneration in MS, in addition to being a target of autoimmune pathology.

FRONTIERS IN CELLULAR NEUROSCIENCE (2021)

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Review Clinical Neurology

Remyelination Trials Are We Expecting the Unexpected?

Alexandr Klistorner et al.

Summary: Neuroaxonal loss is believed to be the main cause of progressive disability in multiple sclerosis, making remyelination a potential neuroprotective strategy. Researchers, regulators, and the pharmaceutical industry should adjust their expectations and designs for remyelination trials appropriately.

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION (2021)

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Article Clinical Neurology

Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis

Nick Cunniffe et al.

Summary: This study established a standardized approach for identifying candidate drugs for repurposing in the treatment of progressive MS. Through expert review and scoring, four treatments were recommended for immediate testing in progressive MS, with additional treatments prioritized for further consideration. This approach offers new possibilities for the treatment of patients with progressive MS.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2021)

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Review Neurosciences

Stem cell derived oligodendrocytes to study myelin diseases

Konstantina Chanoumidou et al.

GLIA (2020)

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Article Biochemistry & Molecular Biology

Protective impacts of erythropoietin on myelinization of oligodendrocytes and schwann cells in CNS and PNS following cuprizone-induced multiple sclerosis- histology, molecular, and functional studies

Jafar Mirzaie et al.

JOURNAL OF CHEMICAL NEUROANATOMY (2020)

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Article Immunology

Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain

Jeroen F. J. Bogie et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Article Immunology

Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis

Maria Ines Cunha et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Article Multidisciplinary Sciences

MAFG-driven astrocytes promote CNS inflammation

Michael A. Wheeler et al.

NATURE (2020)

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Review Neurosciences

Immune cell modulation of oligodendrocyte lineage cells

Emily P. Harrington et al.

NEUROSCIENCE LETTERS (2020)

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Article Multidisciplinary Sciences

Feline irradiated diet-induced demyelination; a model of the neuropathology of sub-acute combined degeneration?

Abigail B. Radcliff et al.

PLOS ONE (2020)

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Article Clinical Neurology

Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions

Nina L. Fransen et al.

BRAIN (2020)

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Article Neurosciences

Regulatory B Cells Normalize CNS Myeloid Cell Content in a Mouse Model of Multiple Sclerosis and Promote Oligodendrogenesis and Remyelination

Andrea Pennati et al.

JOURNAL OF NEUROSCIENCE (2020)

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Article Neurosciences

Astrocytes Are Required for Oligodendrocyte Survival and Maintenance of Myelin Compaction and Integrity

Reshmi Tognatta et al.

FRONTIERS IN CELLULAR NEUROSCIENCE (2020)

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Article Clinical Neurology

Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study

Anna He et al.

LANCET NEUROLOGY (2020)

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Article Cell Biology

Delayed Demyelination and Impaired Remyelination in Aged Mice in the Cuprizone Model

Stefan Gingele et al.

CELLS (2020)

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Article Neurosciences

Motor learning promotes remyelination via new and surviving oligodendrocytes

Clara M. Bacmeister et al.

NATURE NEUROSCIENCE (2020)

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Article Clinical Neurology

Lesion stage-dependent causes for impaired remyelination in MS

Katharina Hess et al.

ACTA NEUROPATHOLOGICA (2020)

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Article Clinical Neurology

Extrinsic immune cell-derived, but not intrinsic oligodendroglial factors contribute to oligodendroglial differentiation block in multiple sclerosis

Laura Starost et al.

ACTA NEUROPATHOLOGICA (2020)

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Review Clinical Neurology

Remyelination in multiple sclerosis: from basic science to clinical translation

Catherine Lubetzki et al.

LANCET NEUROLOGY (2020)

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Article Neurosciences

Regulatory T cells promote remyelination in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis following human neural stem cell transplant

Laura L. McIntyre et al.

NEUROBIOLOGY OF DISEASE (2020)

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Article Neurosciences

Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis

Chotima Boettcher et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2020)

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Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

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Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function

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Activated microglial cells acquire an immature dendritic cell phenotype and may terminate the immune response in an acute model of EAE

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Remyelination capacity of the MS brain decreases with disease chronicity

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Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesions

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Remyelination protects axons from demyelination-associated axon degeneration

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Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis

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Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse

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Article Biochemistry & Molecular Biology

LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis

Sha Mi et al.

NATURE MEDICINE (2007)

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Article Clinical Neurology

Remyelination can be extensive in multiple sclerosis despite a long disease course

R. Patani et al.

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY (2007)

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Article Clinical Neurology

Extensive cortical remyelination in patients with chronic multiple sclerosis

Monika Albert et al.

BRAIN PATHOLOGY (2007)

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Article Clinical Neurology

Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology

Roberta Magliozzi et al.

BRAIN (2007)

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Article Multidisciplinary Sciences

Activation of the subventricular zone in multiple sclerosis: Evidence for early glial progenitors

Brahim Nait-Oumesmar et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2007)

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Article Clinical Neurology

Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

Tanja Kuhlmann et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2007)

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Article Clinical Neurology

Remyelination is extensive in a subset of multiple sclerosis patients

Peter Patrikios et al.

BRAIN (2006)

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Article Clinical Neurology

Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis

I. Coman et al.

BRAIN (2006)

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Article Immunology

The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses

Alexandre Rolland et al.

JOURNAL OF IMMUNOLOGY (2006)

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Article Clinical Neurology

Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis

LA Boven et al.

BRAIN (2006)

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Article Neurosciences

Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation

MR Kotter et al.

JOURNAL OF NEUROSCIENCE (2006)

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Article Biochemistry & Molecular Biology

Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation

SA Back et al.

NATURE MEDICINE (2005)

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Article Clinical Neurology

Axonal signals in central nervous system myelination, demyelination and remyelination

L Coman et al.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2005)

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Article Neurosciences

LINGO-1 negatively regulates myelination by oligodendrocytes

S Mi et al.

NATURE NEUROSCIENCE (2005)

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Review Behavioral Sciences

Evolution of the brain and intelligence

G Roth et al.

TRENDS IN COGNITIVE SCIENCES (2005)

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Article Neurosciences

Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro

R Selvaraju et al.

MOLECULAR AND CELLULAR NEUROSCIENCE (2004)

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Article Clinical Neurology

Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion

MH Barnett et al.

ANNALS OF NEUROLOGY (2004)

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Article Neurosciences

Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan

PH Larsen et al.

JOURNAL OF NEUROSCIENCE (2003)

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Article Neurosciences

Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human

A Craig et al.

EXPERIMENTAL NEUROLOGY (2003)

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Article Clinical Neurology

Efficient central nervous system remyelination requires T cells

AJ Bieber et al.

ANNALS OF NEUROLOGY (2003)

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Article Clinical Neurology

Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time

T Kuhlmann et al.

BRAIN (2002)

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Article Clinical Neurology

Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis?

P Charles et al.

BRAIN (2002)

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Article Clinical Neurology

Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord

G Wolswijk

BRAIN (2002)

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Article Clinical Neurology

Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre

JL Mason et al.

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY (2001)

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Article Neurosciences

NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions

A Chang et al.

JOURNAL OF NEUROSCIENCE (2000)

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Article Pathology

Multiple sclerosis and chronic autoimmune encephalomyelitis -: A comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions

B Kornek et al.

AMERICAN JOURNAL OF PATHOLOGY (2000)

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Article Clinical Neurology

Acute axonal injury in multiple sclerosis -: Correlation with demyelination and inflammation

A Bitsch et al.

BRAIN (2000)

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Article Clinical Neurology

Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis

G Wolswijk

BRAIN (2000)

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Article Clinical Neurology

Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects - Epitope spreading versus clonal persistence

N Goebels et al.

BRAIN (2000)

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