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rHIgM22 enhances remyelination in the brain of the cuprizone mouse model of demyelination.

Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal. Previous studies have sh…

Mechanisms of cell-cell interaction in oligodendrogenesis and remyelination after stroke.

White matter damage is a clinically important aspect of several central nervous system diseases, including stroke. Cerebral white matter pri … r components promote an environment, which is favorable for neural repair, vascular remodeling, and remyelination. For effective remyelination to take place, oligodendrocyte precursor cells (OPCs) play critical roles by proliferating and differentiating into mature oligodendrocytes, which help to decrease the burden of axonal injury. Notably, other types of cel …

Изъятие 6-пирувойл-тетрагидропитерина синтаза способствует ремиэлизации в множестве склерозов.

Множественный склероз (MS) — аутоиммунное заболевание CNS, характеризующееся обезвоживанием, нейроинфламмацией и нейронной потерей. Несмотря на то, что нынешние химиотерапии и иммунотерапии для MS эффективно смягчают болезнь и клинические симптомы, нейрозащита, нацеленная на аксоны/невралигии, по-прежнему носит терапевтический характер. Накопляющиеся данные свидетельствуют о том, что плохое распространение ячеек-прекурсоров олигодендроцитов (ОПК) и последующая миграция/дифференцация существенно препятствуют восстановлению во время НР. Однако молекулярные механизмы, лежащие в основе дисфункции

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a CNS autoimmune disease that is characterized by demyelination, neuroinflammation, and neuronal loss … e precursor cell (OPC) proliferation and subsequent migration/differentiation significantly impedes remyelination during MS. However, the molecular mechanisms underlying OPC dysfunction during MS remain elusive. METHODS: Re-analysis of single-cell sequencing data from human and mouse oligodendrocyte lineage cells (OLCs), along with staining results from brain …

Отличительные транскрипционные изменения отличают эффективность и плохое воспоминание при множественном склерозе.

Множественный склероз (MS) является весьма разнородным заболеванием с разной способностью к ремиелизации между отдельными лицами и между повреждениями. Однако молекулярные механизмы, лежащие в основе потенциала возрождения, по-прежнему плохо понимаются. В этом исследовании мы стремились воспользоваться внутренней гетерогенностью в ремиелионирующих способностях между донорами и повреждениями MS, с тем чтобы обнаружить известные и новейшие проремилинирующие молекулы для лечения MS. Для уточнения различных молекулярных сигнатур, лежащих в основе потенциала ремиилирования, мы стратифицировали доно

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a highly heterogeneous disease, with varying remyelination potential across individuals and between lesions. However, the molecular mechanisms underlying the potential to remyelinate remain poorly understood. In this study, we aimed to take advantage of the intrinsic heterogeneity in remyelinating capacity between MS donors and les…

Nuclear receptor PPARγ targets GPNMB to promote oligodendrocyte development and remyelination.

Myelin injury occurs in brain ageing and in several neurological diseases. Failure of spontaneous remyelination is attributable to insufficient differentiation of oligodendrocyte precursor cells (OPCs) into mature myelin-forming oligodendrocytes in CNS demyelinated lesions. Emerging evidence suggests that peroxisome proliferator-activated receptor γ (PPARγ) is the master gatekeeper of CNS injury and repair and plays an important regulatory role in various neurodegenerative diseases. Although studies demonstrate positive effects of PPARγ in oligodendrocyte ontogeny in vitro, the cell-intrinsic …

Микроглиатоподобные чувствительности ограничивают ремиилизацию через сенсацию, связанную с фенотипом фенория.

Способность регенерировать миелин в центральной нервной системе снижается с возрастом. Это сокращение особенно заметно в случае множественного склероза (MS), хронического заболевания демиелином. Независимо от того, способствует ли клеточная сенсация, являющаяся отличительной чертой старения, нарушению воспоминаний, до сих пор неизвестно. Здесь мы показываем, что яркие клетки накапливаются в демиелинированных повреждениях после травмы, а лечение сенолитами усиливает ремиэлизацию у молодых и средних мышей, но не пожилых мышей. В юных мышах мы наблюдаем за тем, как корректируются стенограммы, свя

Совпадение в аннотации оригинала
The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesi…

Моноцитная система снижает эффективность центральной нервной системы ремиелиции.

Регенерация миелина в центральной нервной системе (СНС) восстанавливает нервное здоровье и функции, однако снижение ее эффективности в результате старения и развития нейродегенеративных заболеваний ведет к потере аксона и/или дегенерации. Несмотря на то, что миелиоидные клетки CNS были причастны к регулированию эффективности ремиелиции, не ясно, какой конкретный вклад вносят моноциты крови по сравнению с микроглией. Здесь мы обнаруживаем, что моноциты выполняют функции, не связанные с избытком, по сравнению с микроглией в регулировании ремиэлизации. Используя трансгенную мышь, в которой класси

Совпадение в аннотации оригинала
The regeneration of myelin in the central nervous system (CNS) reinstates nerve health and function, yet its decreased efficiency with aging and progression of neurodegenerative disease contributes to axonal loss and/or degeneration. Although CNS myeloid cells have been implicated in regulating the efficiency of remyelination, the distinct contribution of bl…

Однократная внутрицеребральная агонистическая инъекция TNFR2 оказывает воздействие на воспроизводство в модели кухонной зоны.

Согласно прогнозам, развитие терапевтических средств, которые улучшают регенерацию миелиновых оболочек после демиелинации, предотвратит нейродегенерацию. Обнадеживающей целью, направленной на усиление ремии, является фактор некроза опухоли иммуномумудулятору (TNFα) и его рецепторы TNFR1 и TNFR2. TNFR2 на олигодендроцитных линейных клетках и микроглии координирует различные защитные функции, такие, как распространение олигодендроцитных потомков, выживание зрелых олигодендроцитов и высвобождение противовоспалительных цитокинов в животных моделях воспаления и обезвоживания. Здесь, в модели чашезо

Совпадение в аннотации оригинала
The development of therapeutics that enhances the regeneration of myelin sheaths following demyelination is predicted to prevent neurodegeneration. A promising target to enhance remyelination is the immunomodulatory cytokine tumor necrosis factor alpha (TNFα) and its receptors TNFR1 and TNFR2. TNFR2 on oligodendrocyte lineage cells and microglia coordinates …

GCPII Inhibition Promotes Remyelination after Peripheral Nerve Injury in Aged Mice.

Peripheral nerve injuries (PNIs) represent a significant clinical challenge, particularly in elderly populations where axonal remyelination and regeneration are impaired. Developing therapies to enhance these processes is crucial for improving PNI repair outcomes. Glutamate carboxypeptidase II (GCPII) is a neuropeptidase that plays a pivotal role in modulating glutamate signaling through its enzymatic cleavage of the abundant neuropeptide N-acetyl aspartyl glutamate (NAAG) to liberate glutamate. Within the PNS, GCPII is expressed in Schwann cells and activated macrophages, and its expression i…

Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.

BACKGROUND AND OBJECTIVES: Siponimod is an oral, selective sphingosine-1-phosphate receptor-1/5 modulator approved for treatment of multiple sclerosis. METHODS: Mouse MRI was used to investigate remyelination in the cuprizone model. We then used a conditional demyelination Xenopus laevis model to assess the dose-response of siponimod on remyelination. In experimental autoimmune encephalomyelitis-optic neuritis (EAEON) in C57Bl/6J mice, we monitored the retinal thickness and the visual acuity using optical coherence tomography and optomotor response. Optic nerve inflammatory infiltrates, demye…

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

OBJECTIVE: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response - measured by change in magnetisat…

Icariin enhances remyelination process after acute demyelination induced by cuprizone exposure.

Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remi … ical changes in the brains. CPZ administration for 5 weeks resulted in completely demyelination and remyelination occurred when CPZ was withdrawn. ICA treatment during the recovery period for 1 week significantly improved myelin restoration, enhanced NF200-positive axons repair, increased the number of APC+/Olig2+ mature oligodendrocytes and prevented neuron-de …

Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination.

Myelin, which is a multilamellar structure that sheathes the axon, is essential for normal neuronal function. In the central nervous system … . Furthermore, Myo1d knockdown treatment increased pro-inflammatory microglia and astrocytes during remyelination. In contrast, anti-inflammatory microglia were decreased. The percentage of caspase 3-positive cells in total CC1-positive OLs were also increased by Myo1d knockdown. These results indicated that Myo1d plays an important role during the regeneration …

Nuclear factor-κB activation in Schwann cells regulates regeneration and remyelination.

Schwann cells (SCs) are crucial for peripheral nerve development and regeneration; however, the intrinsic regulatory mechanisms governing po … ration was impaired at 31 days and significantly enhanced at 65 days in transgenic animals. Compact remyelination and Remak bundle organization were significantly compromised at 31 days and restored by 65 days post injury. Together, these data indicate that inhibition of NF-κB activation in SCs transiently delays axonal regeneration and compact remyelination. M …

Partial inhibition of proteasome activity enhances remyelination after cuprizone-induced demyelination.

We have previously demonstrated that addition of low concentrations of lactacystin (a specific inhibitor of the proteasome) to oligodendrogl … crease in proteasome activity induced by the injection of lactacystin in the corpus callosum in the remyelination process that normally occurs after cuprizone-induced demyelination. This treatment markedly improves the remyelination process that normally occurs in cuprizone-induced demyelination. It also attenuates the activation of NFkappaB and the recruitment …

Meningeal cells enhance limited CNS remyelination by transplanted olfactory ensheathing cells.

Olfactory ensheathing cells (OECs) are candidate cells for transplant-mediated repair of persistent demyelination in diseases such as multip … the basis of low-affinity nerve growth factor receptor (p75) expression, results in less extensive remyelination than an unpurified preparation following transplantation into areas of persistent demyelination in rodent CNS in the X-irradiation/ethidium bromide (X-EB) model. A distinctive feature of the unpurified preparation both in vitro and following transpl …

Temporal Dynamics of CNS Cholesterol Esters Correlate with Demyelination and Remyelination.

Elevated cholesterol ester levels have been observed in the CNS of patients with neurological diseases; yet, the source of cholesterol ester accumulation and whether it is directly linked to demyelination remain undefined. This study investigates the temporal dynamics of cholesterol esters using the Plp1-iCKO-Myrf mouse model, which features distinct phases of demyelination and remyelination. Our findings reveal that cholesterol ester levels increased with demyelination in both the brain and spinal cord. In the brain, cholesterol esters declined to normal levels during remyelination, whereas c…

Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.

Oligodendrocytes, the myelinating cells in the central nervous system, are implicated in several neurological disorders marked by dysfunctional RNA-binding proteins (RBPs). The present study aimed at investigating the role of hnRNP A1 in the proteome of the corpus callosum, prefrontal cortex, and hippocampus of a murine cuprizone-induced demyelination model. Right after the cuprizone insult, we administered an hnRNP A1 splicing activity inhibitor and analyzed its impact on brain remyelination by nanoESI-LC-MS/MS label-free proteomic analysis to assess the biological processes affected in these…

Понимание сложности клеточных механизмов в воссоединении: роль циркадийского ритма.

Термин "круглый ритм" относится к 24-часовым колебаниям, встречающимся в различных физиологических процессах в организмах, которые отвечают за поддержание гомеостаза. Многие неврологические заболевания связаны главным образом с процессом обезвоживания, а ремиелинация имеет решающее значение для лечения неврологических заболеваний. Текущие исследования сосредоточены главным образом на ключевой роли циркадских часов в патофизиологических механизмах множественного склероза. Различные исследования показали, что циркадийский ритм регулирует различные клеточные молекулярные механизмы и сигнальные пу

Совпадение в аннотации оригинала
The term "circadian rhythm" refers to the 24-h oscillations found in various physiological processes in organisms, responsible for maintaining bodily homeostasis. Many neurological diseases mainly involve the process of demyelination, and remyelination is crucial for the treatment of neurological diseases. Current research mainly focuses on the key role of c…