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Выявление биомаркеров для ремилеляции и восстановления при многоразовом склерозе: показатель прогресса.

Фон: Множественная патология склероза (MS) характеризуется острым и хроническим воспалением, обезвоживанием, аксоновой травмой и нейродегенерацией. После десятилетий исследований по проблеме дегенерации, связанной с НР, недавние усилия сместились в направлении восстановления и предотвращения дальнейшего ущерба. Одним из ключевых направлений деятельности является процесс ремиэлизации, в рамках которого исследователи изучают воздействие фармакотерапии на механизмы ремонта миелина. Множественные соединения испытываются на предмет их способности содействовать воссоединению в различных клинических

Совпадение в аннотации оригинала
Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, and neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery and the prevention of further damage. A key area of focus is the remyelination process, where researchers are…

Identification of the Lipid Antigens Recognized by rHIgM22, a Remyelination-Promoting Antibody.

Failure of the immune system to discriminate myelin components from foreign antigens plays a critical role in the pathophysiology of multiple sclerosis. In fact, the appearance of anti-myelin autoantibodies, targeting both proteins and glycolipids, is often responsible for functional alterations in myelin-producing cells in this disease. Nevertheless, some of these antibodies were reported to be beneficial for remyelination. Recombinant human IgM22 (rHIgM22) binds to myelin and to the surface of O4-positive oligodendrocytes, and promotes remyelination in mouse models of chronic demyelination. …

Fractalkine enhances oligodendrocyte regeneration and remyelination in a demyelination mouse model.

Demyelinating disorders of the central nervous system (CNS) occur when myelin and oligodendrocytes are damaged or lost. Remyelination and regeneration of oligodendrocytes can be achieved from endogenous oligodendrocyte precursor cells (OPCs) that reside in the adult CNS tissue. Using a cuprizone mouse model of demyelination, we show that infusion of fractalkine (CX3CL1) into the demyelinated murine brain increases de novo oligodendrocyte formation and enhances remyelination in the corpus callosum and cortical gray matter. This is achieved by increased OPC proliferation in the cortical gray mat…

Effect of Sox10 on remyelination of the hippocampus in cuprizone-induced demyelinated mice.

OBJECTIVE: The low number of oligodendrocytes (OLs) in the hippocampus of patients with schizophrenia suggests that hippocampal demyelinatio … into the hippocampus after establishing the demyelinating model to investigate effects of Sox10 on remyelination. RESULTS: CPZ mice showed abnormal behavioral changes, a large number of pathological changes in the myelin sheaths, and significantly reduced protein expression of the myelin sheath markers myelin basic protein and proteolipid protein. This confir …

Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination.

Myelin sheaths play important roles in neuronal functions. In the central nervous system (CNS), the myelin is formed by oligodendrocytes (OLs), which are differentiated from oligodendrocyte precursor cells (OPCs). In CNS demyelinating disorders such as multiple sclerosis (MS), the myelin sheaths are damaged and the remyelination process is hindered. Small molecule drugs that promote OPC to OL differentiation and remyelination may provide a new way to treat these demyelinating diseases. Here we report that donepezil, an acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzhe…

MiR-146a promotes remyelination in a cuprizone model of demyelinating injury.

The death of mature oligodendrocytes (OLs) which are the sole myelinating cells of the central nervous system (CNS), leads to demyelination and functional deficits. Currently, there is lack of effective remyelination therapies for patients with demyelinating diseases. MicroRNAs (miRNAs) mediate OL function. We hypothesized that miR-146a, by inactivating interleukin-1 receptor-associated kinase 1 (IRAK1), promotes differentiation of oligodendrocyte progenitor cells (OPCs) and thereby enhances remyelination. To test this hypothesis, a demyelination model induced by a cuprizone (CPZ) diet was emp…

A monoclonal natural human IgM protects axons in the absence of remyelination.

BACKGROUND: Whereas demyelination underlies early neurological symptoms in multiple sclerosis (MS), axonal damage is considered critical for … ogressive MS using multiple reparative readouts. The minimum effective dose is similar to that of a remyelination-promoting monoclonal human IgM discovered by our group that is presently in clinical trials for MS.

Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination.

Permanent damage to white matter tracts, comprising axons and myelinating oligodendrocytes, is an important component of brain injuries of t … promoting β-catenin degradation. We found that Axin2 function was essential for normal kinetics of remyelination. The small molecule inhibitor XAV939, which targets the enzymatic activity of tankyrase, acted to stabilize Axin2 levels in OLPs from brain and spinal cord and accelerated their differentiation and myelination after hypoxic and demyelinating injury. …

Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves.

BACE1 is a promising therapeutic and preventive target for Alzheimer's disease because it is essential for amyloid deposition. However, the recent demonstration of BACE1 in modulating developmental myelination in both peripheral and central nervous systems raises a concern of its effect on myelin maintenance or remyelination, and inhibition of these processes will potentially be detrimental to the BACE1 inhibitor users who are susceptible to myelination diseases such as adult peripheral nerve injury or multiple sclerosis. In this report, we investigated the role of BACE1 during peripheral nerv…

KDM2B-PP1 Promotes Remyelination and Functional Recovery After Facial Nerve Injury.

BACKGROUND: Peripheral nerve injury (PNI) often causes persistent sensory and motor deficits because of incomplete axonal regeneration and insufficient remyelination. Schwann cells (SCs) are essential for peripheral nerve repair, but effective recovery depends on their timely transition from a repair state to a myelinating phenotype. OBJECTIVE(S): To investigate whether KDM2B-PP1, a bioactive peptide designed to disrupt the interaction between lysine-specific demethylase 2B (KDM2B) and enhancer of zeste homologue 2 (EZH2), promotes SC redifferentiation, remyelination, and functional recovery …

CSF1R inhibition following antibody mediated demyelination has limited impact on remyelination.

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system. B cell depleting treatments are … -dependent and resolved over four weeks. Because of the previously described impact of microglia on remyelination, we targeted microglia depletion with CSF1R inhibition to test their role in this model. Despite a significant reduction in total microglia following CSF1R inhibition, microglia or macrophage density was high in recovering lesions. Premyelinating ol …

Evaluating remyelination compounds for new applications in opioid use disorder management.

Opioid use disorder (OUD) is associated with a reduction in brain white matter, affecting critical areas involved in decision-making, impulse control, and reward processing. The FDA has approved several drugs and natural compounds that enhance myelination, targeting oligodendrocyte progenitor cells (OPCs), directly enhancing oligodendrocyte (OL) function, or acting as cofactors for myelin production. This retrospective case study aimed to assess whether current clinical evidence supports the use of myelin-enhancing agents to promote remission in OUD. We evaluated a range of compounds with demo

Remyelination of chronic demyelinated lesions with directly induced neural stem cells.

The limited ability of CNS progenitor cells to differentiate into oligodendrocytes limits the repair of demyelinating lesions and contributes to the disability of people with progressive multiple sclerosis (PMS). Neural stem cell (NSC) transplantation has emerged as a safe therapeutic approach in people with PMS, where it holds the promise of healing the injured CNS. However, the mechanisms by which NSC grafts could promote CNS remyelination need to be carefully assessed before their widespread clinical adoption. In this study, we used directly induced NSCs (iNSCs) as a novel transplantation s…

EAAT3 Модификация: Потенциальный новый путь к ремиэлизации в множестве склерозов.

Модификацию переносчика аминокислот 3 (ЕААТ3) можно рассматривать в качестве нового подхода к лечению множественного склероза (МС). EAAT3 играет ключевую роль в регулировании окислительного стресса и функции олигодендроцита благодаря его способности перевозить циштейн, ограничивающий скорость строительного блока в синтезе антиоксидантного глютатиона. Таким образом, по гипотезе активация EAAT3 позволяет улучшить здоровье олигодендроцитов и облегчить их дифференциационный блок в MS, улучшив потенциал ремиэлирования. С использованием модели демиэлизации, вызванной кубической зоной, было изучено в

Совпадение в аннотации оригинала
Modulating the excitatory amino acid transporter 3 (EAAT3) can be considered a novel approach for the treatment of multiple sclerosis (MS). … pothesised to improve oligodendrocyte health and relieve its differentiation block in MS, improving remyelination capacity. Using a cuprizone-induced demyelination model, the effects of EAAT3 overexpression by viral transduction of oligodendrocytes and pharmacological inhibition of EAAT3 were examined. Surprisingly, EAAT3 overexpression significantly hampered r …

Targeting Remyelination in Spinal Cord Injury: Insights and Emerging Therapeutic Strategies.

INTRODUCTION: Spinal cord injury (SCI) is a severe neurological disease characterized by significant motor, sensory, and autonomic dysfunctions. SCI is a major global disability cause, often resulting in long-term neurological impairments due to the impeded regeneration and remyelination of axons. A SCI interferes with communication between the brain and the spinal cord networks that control neurological functions. Recent advancements in understanding the molecular and cellular mechanisms of remyelination have opened novel therapeutic interventions. METHOD: This review systematically sourced …

Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination.

The brain's endogenous capacity to restore damaged myelin deteriorates during the course of demyelinating disorders. Currently, no treatment options are available to establish remyelination. Chronic demyelination leads to damaged axons and irreversible destruction of the central nervous system (CNS). We identified two promising therapeutic candidates which enhance remyelination: oncostatin M (OSM), a member of the interleukin-6 family, and downstream mediator tissue inhibitor of metalloproteinases-1 (TIMP-1). While remyelination was completely abrogated in OSMRβ knockout (KO) mice, OSM overexp…

Defective cholesterol clearance limits remyelination in the aged central nervous system.

Age-associated decline in regeneration capacity limits the restoration of nervous system functionality after injury. In a model for demyelination, we found that old mice fail to resolve the inflammatory response initiated after myelin damage. Aged phagocytes accumulated excessive amounts of myelin debris, which triggered cholesterol crystal formation and phagolysosomal membrane rupture and stimulated inflammasomes. Myelin debris clearance required cholesterol transporters, including apolipoprotein E. Stimulation of reverse cholesterol transport was sufficient to restore the capacity of old mic

Electrical stimulation enhanced remyelination of injured sciatic nerves by increasing neurotrophins.

Previous studies have demonstrated that electrical stimulation (ES) enhances axonal regeneration following central and peripheral nerve injury. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less, and the mechanism underlying its action remains unclear. In the present study, neuron/Schwann cell (SC) co-cultures in vitro and crush-injured sciatic nerves in rats were subjected to 1 h of continuous ES (20 Hz, 100 micros, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The exp…

Pioglitazone promotes peripheral nerve remyelination after crush injury through CD36 upregulation.

In our previous study, we found that CD36-deficient mice showed significant delays in peripheral nerve remyelination after sciatic nerve crush injury and suggested that CD36 played an important role in the restoration of injured peripheral nerves. The aim of this study was to investigate whether CD36 upregulation can promote peripheral nerve remyelination. We made crush injury that caused demyelination and mild axonal degeneration to sciatic nerves and investigated the effect of pioglitazone (PIO) on the remyelination post-injury in C57Bl/6 wild-type and CD36-deficient mice. The immunohistoche…

Angiotensin II impairs the remyelination mediated by brain endothelial cell-derived exosomes.

White matter hyperintensities (WMH), characterized by myelin loss and axonal injury, are largely driven by hypertension, their most significant modifiable risk factor. The role of endothelial cell-derived exosomes (EC-Exos) in oligodendrocyte precursor cell (OPCs)-mediated remyelination within WMH remains critical but poorly defined. This study investigated the function of EC-Exos in remyelination by comparing exosomes from angiotensin II-treated brain microvascular endothelial cells (AngII-Exos; modeling hypertensive conditions) with those from untreated cells (BMEC-Exos; modeling normotensiv…