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Aurka-Bhlhe41 axis prevents premature aging-like microglial dysfunction and promotes remyelination.

Aging accelerates central nervous system remyelination failure and neurodegeneration. Microglia promote remyelination by phagocytosing myelin debris, but this function is impaired by aging-related CD22 upregulation. However, the molecular mechanisms counteracting premature aging-related microglial dysfunction and remyelination impairment remain unclear. Here, we report that Aurka-Bhlhe41 axis prevents premature aging-like microglial dysfunction and promotes remyelination by restraining progressive CD22 upregulation. We identified that microglia-enriched Bhlhe41 was negatively autoregulated and…

Complement inhibition rapidly blocks lesion extension and facilitates remyelination in neuromyelitis optica.

Cumulative disability in neuromyelitis optica spectrum disorder (NMOSD) results from incomplete recovery following inflammatory, demyelinating attacks. Retrospective case studies and current clinical practice indicate that rapid treatment of acute attacks with apheresis limits injury and improves recovery. We evaluated the effects of apheresis and complement inhibition on lesion progression and recovery in a murine ex vivo cerebellar explant model of NMOSD injury. While both strategies reduced lesion formation relative to vehicle treatment, we observed that anti-C5 complement inhibition with e

Interventions promoting remyelination in multiple sclerosis: a systematic review of clinical trials.

OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal damage. Current therapies primarily manage symptoms and slow disease progression but do not achieve remyelination. This systematic review evaluates the efficacy and safety of remyelination-promoting interventions in MS, focusing on clinical trials utilizing outcome measures validated in prior studies as indicators of remyelination. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was conducted in May 2024. Cl…

Фитогормонная абсциозная кислота усиливает ремиелионацию в мышиных моделях множественного склероза.

ВВЕДЕНИЕ: За последние несколько десятилетий в западных странах произошел внезапный рост числа случаев множественного склероза (МС). Однако нынешние методы лечения часто демонстрируют ограниченную эффективность у некоторых пациентов и связаны с неблагоприятными последствиями, что подчеркивает необходимость более безопасных и эффективных терапевтических подходов. Было отмечено, что важную роль в развитии НР играют экологические факторы, в частности привычки питания. В этом исследовании мы первыми исследуем потенциальное защитное воздействие гибридной кислоты (ABA) в MS. АБА, которая изобилие вс

Совпадение в аннотации оригинала
INTRODUCTION: Over the past few decades, there has been a sudden rise in the incidence of Multiple Sclerosis (MS) in Western countries. Howe … Alzheimer's disease. METHODS: In this study, we investigated whether ABA supplementation enhances remyelination in both ex vivo and in vivo mouse models. RESULTS: Our results indicated that ABA enhanced remyelination and that this enhanced remyelination is associated with increased lipid droplet load, reduced levels of degraded myelin, and a higher abundance …

EAAT3 impedes oligodendrocyte remyelination in chronic cerebral hypoperfusion-induced white matter injury.

BACKGROUND: Chronic cerebral hypoperfusion-induced demyelination causes progressive white matter injury, although the pathogenic pathways ar … njury. IF, Luxol Fast Blue staining, and electron microscopy were used to investigate the effect of remyelination. 5-Ethynyl-2-Deoxy Uridine staining, transwell chamber assays, and IF were used to examine the effects of OPCs' proliferation, migration, and differentiation in vivo and in vitro. The novel object recognition test, the Y-maze test, the rotarod test, …

Anti-LINGO-1 improved remyelination and neurobehavioral deficit in cuprizone-induced demyelination.

OBJECTIVES: Central nervous system demyelination is the main feature of multiple sclerosis (MS). The most important unmet need in MS is use of treatments that delay the progression of the disease. Leucine-rich repeat and Immunoglobulin-like domain containing NOGO receptor-interacting protein 1(LINGO-1) have been known as inhibitors of oligodendrocyte differentiation and myelination. MATERIALS AND METHODS: We investigated LINGO-1 antibody effects on remyelination and neurobehavioral deficit using cuprizone-induced demyelination. Animals were randomly divided into three groups (n = 10): (1) Con…

Connexin 43 deletion in astrocytes promotes CNS remyelination by modulating local inflammation.

As the most abundant gap junction protein in the central nervous system (CNS), astrocytic connexin 43 (Cx43) maintains astrocyte network homeostasis, affects oligodendroglial development and participates in CNS pathologies as well as injury progression. However, its role in remyelination is not yet fully understood. To address this issue, we used astrocyte-specific Cx43 conditional knockout (Cx43 cKO) mice generated through the use of a hGFAP-cre promoter, in combination with mice carrying a floxed Cx43 allele that were subjected to lysolecithin so as to induce demyelination. We found no signi…

4-Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury.

Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4-aminopyridine … urther studies demonstrated that 4-AP also enhanced recovery of nerve conduction velocity, promoted remyelination, and increased axonal area post-injury. We additionally found that 4-AP treatment enables distinction between incomplete and complete lesions more rapidly than existing approaches, thereby potentially addressing the critical challenge of more effect …

Metformin Attenuates Cognitive Impairments in Hypoxia-Ischemia Neonatal Rats via Improving Remyelination.

Perinatal hypoxia-ischemia (H/I) causes brain injury and myelination damage. Finding efficient methods to restore myelination is critical for the recovery of brain impairments. By applying an H/I rat model, we demonstrate that metformin (Met) treatment significantly ameliorates the loss of locomotor activity and cognition of H/I rat in the Morris water maze and open field task tests. After administration of Met to H/I rat, the proliferation of Olig2+ oligodendrocyte progenitor cells and the expression of myelin basic protein are obviously increased in the corpus callosum. Additionally, the mye

Molecular Mediators Associated With Myelination, Demyelination, and Remyelination in the Peripheral Nervous System.

The peripheral nervous system (PNS) is responsible for innervating all regions of the body outside of the central nervous system (CNS), the latter consisting of the brain, spinal cord, and optic nerves. While myelin is an essential component for the efficient functioning of both CNS and peripheral nerve cells, it is particularly important for PNS neurons since their cell bodies lie at considerable distances from their innervated targets. As such, regulation of myelin content and formation in the PNS is a carefully controlled process that involves many cellular and molecular players. The periph

Воздействие нового биотинового соединения в гиппокампальной ремиилизации в крысах.

Обезвоживание обычно наблюдается в нейродегенеративных расстройствах, включая множественный склероз (MS). Добавление биотина, как известно, стабилизирует прогрессирование MS. Чтобы уменьшить эффективную дозу биотина, мы синтезировали новую и превосходящую форму биотина, комплекс магния, который ионологически связан биотином (MgB), и сравнили его зависимое от дозы воздействие с биотином в одиночку после демиелинации с использованием лизолицитина (LPC) у крыс. Myelination была оценена с помощью быстрого синего пятна и иммуностаза от белка MBP, что свидетельствует о том, что наиболее значительное

Совпадение в аннотации оригинала
Demyelination is commonly observed in neurodegenerative disorders, including multiple sclerosis (MS). Biotin supplementation is known to sta … uxol fast blue staining and immunostaining against MBP protein, revealing that the most significant remyelination occurred in the MgB groups. Additionally, both biotin and MgB-treated animals showed dose-dependent improvements in spatial memory. Moreover, we detected a decrease in inflammatory proteins in both treatment groups, which was more prominent in high- …

Remyelinating Drugs at a Crossroad: How to Improve Clinical Efficacy and Drug Screenings.

Axons wrapped around the myelin sheath enable fast transmission of neuronal signals in the Central Nervous System (CNS). Unfortunately, myelin can be damaged by injury, viral infection, and inflammatory and neurodegenerative diseases. Remyelination is a spontaneous process that can restore nerve conductivity and thus movement and cognition after a demyelination event. Cumulative evidence indicates that remyelination can be pharmacologically stimulated, either by targeting natural inhibitors of Oligodendrocyte Precursor Cells (OPCs) differentiation or by reactivating quiescent Neural Stem Cells…

Effects of EHP-101 on inflammation and remyelination in murine models of Multiple sclerosis.

Multiple Sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes in the spinal cord and the brain. … idence that EHP-101 showed potent anti-inflammatory activity, prevented demyelination, and enhanced remyelination. Therefore, EHP-101 represents a promising drug candidate for the potential treatment of different forms of MS.

A case of chronic asymptomatic central pontine myelinolysis with histological evidence of remyelination.

Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the pons. Although usually associated with rapid correction of hyponatremia, CPM may occur despite normonatremia, is often associated with chronic alcoholism and may be asymptomatic. Histological confirmation of asymptomatic CPM is rare. We describe an unusual post-mortem case of extensive but asymptomatic CPM in a chronic alcoholic patient with normonatremia. The affected part of the pons contained thinly myelinated axons with appearances supporting remyelination. We suggest that remyelination may account for the su…

Hes3 expression in the adult mouse brain is regulated during demyelination and remyelination.

Hes3 is a component of the STAT3-Ser/Hes3 Signaling Axis controlling the growth and survival of neural stem cells and other plastic cells. Pharmacological activation of this pathway promotes neuronal rescue and behavioral recovery in models of ischemic stroke and Parkinson's disease. Here we provide initial observations implicating Hes3 in the cuprizone model of demyelination and remyelination. We focus on the subpial motor cortex of mice because we detected high Hes3 expression. This area is of interest as it is impacted both in human demyelinating diseases and in the cuprizone model. We repo…

Axonal and Schwann cell BACE1 is equally required for remyelination of peripheral nerves.

Inhibition of β-site APP cleaving enzyme 1 (BACE1) is being pursued as a therapeutic target for treating patients with Alzheimer's disease because BACE1 is the sole β-secretase for generating β-amyloid peptide. Knowledge regarding the other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination in injured sciatic nerves. Since BACE1 is expected to be ubiquitously expressed, we asked whether axonal or Schwann cell BACE1 is required for optimal remyelina…

Axonal neuregulin 1 is a rate limiting but not essential factor for nerve remyelination.

Neuregulin 1 acts as an axonal signal that regulates multiple aspects of Schwann cell development including the survival and migration of Schwann cell precursors, the ensheathment of axons and subsequent elaboration of the myelin sheath. To examine the role of this factor in remyelination and repair following nerve injury, we ablated neuregulin 1 in the adult nervous system using a tamoxifen inducible Cre recombinase transgenic mouse system. The loss of neuregulin 1 impaired remyelination after nerve crush, but did not affect Schwann cell proliferation associated with Wallerian degeneration or…

Knockout of TLR4 and TLR2 impair the nerve regeneration by delayed demyelination but not remyelination.

BACKGROUND: Knockout of either toll-like receptor 4 (TLR4) or 2 (TLR2) had been reported to delay the Wallerian degeneration after peripheral nerve injury by deterring the recruitment of the macrophages and clearance of myelin debris. However, the impact on the remyelination process is poorly understood. In this study, the effect of TLR2 and TLR4 knockout on the nerve regeneration and on the remyelination process was studied in a mouse model of sciatic nerve crush injury. RESULTS: A standard sciatic nerve crush injury by a No. 5 Jeweler forcep for consistent 30 seconds was performed in Tlr4-/…

Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives.

Peripheral nerve injury (PNI) affects 13-23 individuals per 100,000 annually, and functional recovery hinges on faithful remyelination of regenerating axons by Schwann cells (SCs). This review integrates the complete molecular logic governing the transition from injury-induced SC plasticity to mature myelin regeneration. The hierarchical transcriptional program-from SOX10 pioneer factor engagement through OCT6-mediated promyelinating transition to KROX20/EGR2-driven activation of compact myelin genes-and the instructive role of axonal Neuregulin-1 Type III signaling are dissected. Wallerian de…

Pinch-mediated signaling controls myelination and remyelination in the peripheral nervous system.

During the development of the peripheral nervous system, Schwann cells rely on intricate interactions among extracellular matrix proteins, i … ons and maturation of Remak bundles, Pinch2 modulates myelin thickness and is crucial for effective remyelination following sciatic nerve injury. Our data suggest that Pinch1-mediated specific modulation of Rho GTPase signaling is essential for sorting of axon bundles, and that Pinch2 likely modulates RhoA to relieve its inhibitory effect on myelination and rem …