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The human TIMP-1 unbound structure provides a platform for fragment screening.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a critical regulator of extracellular matrix remodelling and an important mediator of remyelination in demyelinating disorders such as multiple sclerosis. In addition, TIMP-1 has emerged as a promising therapeutic target in cancer due to its interaction with CD63, which promotes tumorigenic signalling and carcinogenesis. Although several structures of TIMP-1 bound to matrix metalloproteinases have been reported, no unbound structure with all druggable sites available has previously been reported. Here, we present the first unbound crystal st…

Electrical Stimulation and Platelet-Rich Plasma as Complementary Approaches for Peripheral Nerve Regeneration.

Peripheral nerve injuries (PNIs) remain a major cause of long-term disability, with standard treatments such as microsurgical repair and autologous grafting often yielding incomplete recovery due to slow axonal regeneration, fibrotic scarring, and limited reinnervation. Emerging therapies, including electrical stimulation (ES) and platelet-rich plasma (PRP), have shown promise but remain insufficient as standalone interventions. ES enhances axonal elongation, remyelination, and neuroplasticity by upregulating regeneration-associated genes and neurotrophins, while PRP delivers autologous growth…

Sciatic Nerve Regeneration in Rat Model With PLGA-MWCNT Conduit Loaded by Fibrin Hydrogel Containing Nanolycopene and Schwann Cells.

This study developed a biodegradable neural guidance conduit using electrospun poly(lactic-co-glycolic acid) (PLGA) and multiwall carbon nan … xylin-eosin/Luxol fast blue) and walking-footprint analysis confirmed enhanced axonal alignment and remyelination. These results highlight the conduit's dual functionality as a structural scaffold and bioactive delivery system for nerve repair.

Dual-network hyaluronic acid hydrogel incorporating FGF21 and layered black phosphorus nanosheets for anti-ferroptosis therapy in spinal cord injury.

Ferroptosis-induced oxidative stress triggers mitochondrial damage in spinal cord injury (SCI), impairing residual neuronal function and dri … suggested that the composite ADBF hydrogels can effectively promote functional repair by enhancing remyelination, accelerating axonal regeneration, inhibiting neurons ferroptosis and regulating immune microenvironment of nerve regeneration. Mechanistically, ADBF attenuates ferroptosis by restoring mitochondrial function via the AMPK/AKT signaling axis, consequ …

A review of multiple sclerosis: From pathophysiology to latest therapeutic advances.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration within the cent … steroids, focus on managing relapses and reducing long-term disability. Novel therapies, including remyelination and neuroprotective agents, are showing promise in advancing care. While these medications can slow progression and improve quality of life, MS remains an incurable disease that requires ongoing research to find more effective therapies. Surgical in …

Оспемифен, селективный модулятор эстрогенного рецептора, усиливает олигодендроцитную миелинизацию и резервирует нейрофункции от травм.

Недостаточность миелиногенеза в результате травм центральной нервной системы (КНС) является хорошо задокументированной патологической особенностью различных заболеваний, таких, как травма белых веществ (ВМИ) и множественный склероз (МС). Реорганизация разрешенных УЛХ лекарственных средств, способных содействовать дифференциации олигодендроцитов (ОИ), представляет собой реалистичный и осуществимый подход к ремонту и функциональному восстановлению миелина. В этом исследовании сообщается, что оспемифен, одобренный УЛХ избирательного модулятора рецептора эстрогена (SERM), в значительной степени сп

Совпадение в аннотации оригинала
Insufficient myelinogenesis following central nervous system (CNS) injuries is a well-documented pathological feature in various diseases, s … eterioration in a dose-dependent manner and benefited myelin regeneration. To confirm the effect on remyelination, toxin-induced demyelination mice, injected with lysophosphatidylcholine into the corpus callosum, were treated with ospemifene. This treatment increased newly generated myelin sheaths in the lesions, confirming its promyelinogenesis effect. Togethe …

Понимание глиальных клеток: последствия для множественных патогенеза склероза и терапии.

Множественный склероз тесно связан с дисфункцией глиальных клеток и сосредоточен на астроцитах, олигодендроцитах и микроглии. В Индии возросло число случаев множественного склероза, однако диагностика и лечение также остаются одним из факторов, серьезно сказывающихся на социальных обязанностях пациента и его благополучии в семье. Серьезная инвалидность и когнитивное расстройство предсказывают потерю работы, снижение уровня жизни. Эти клетки играют важную роль в поддержании нормального гомеостазиса и содействии нейрональной активности, а также вносят значительный вклад в нейроинфламацию. Глиаль

Совпадение в аннотации оригинала
Multiple sclerosis has been closely related to the dysfunction of Glial cells, focusing on astrocytes, oligodendrocytes, and microglia. The … pies and symptomatic management, address novel tactics aimed at glial cells, namely in the areas of remyelination and immunomodulation. A robust literature survey underlines the significance of comprehending the complex interplay between glial cells and the immune system in multiple sclerosis, indicating that this insight may facilitate more targeted and indivi …

Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush.

MicroRNA (miRNA) has great potential to treat a wide range of illnesses by regulating the expression of eukaryotic genes. Biomaterials with … mplexes significantly promoted nerve regeneration after sciatic nerve crush, specifically enhancing remyelination. All these results show that the use of PDAPEI to deliver miR-221/222 may provide a safe therapeutic means of treating nerve crush injury and may help to overcome the barrier of biomaterial toxicity and low efficiency often encountered during medica …

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone-Induced Central Nervous System Demyelination.

AIM AND METHODS: Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells. With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination. RESULTS: The synthetic cannabinoid agonist WIN55212.2 at 1 μM increased the myelin basic protei…

Multiple sclerosis: the role of melatonin and N-acetylserotonin.

Multiple sclerosis (MS) is an immune mediated disorder that is under intensive investigation in an attempt to improve on available treatment … partly via increased oxidative phosphorylation. Melatonin also inhibits demyelination and increases remyelination, suggesting that its local regulation in white matter astrocytes by serotonin availability and apolipoprotein E4, among other potential factors, will be important in the etiology, course and treatment of MS. Here we review the role of local melatoni …

Clinical analysis and outcomes of amyotrophic lateral sclerosis with demyelinating polyneuropathy.

Abnormalities of both motor and sensory nerve action potentials, similar to those found in demyelinating polyneuropathy, may occur in patien … ginal reduction in myelin thickness, and teased fiber analysis revealed segmental demyelination and remyelination, but axonal degeneration was found in one patient. The mean interval from disease onset to respiratory failure or death in our three patients and seven previously documented ALS patients with DPN was 43.1 ± 18.7 months. Our findings suggest that sur …

Proliferating immature Schwann cells contribute to nerve regeneration after ischemic peripheral nerve injury.

Schwann cells exhibit a high degree of plasticity in adult peripheral nerves after mechanical injury; they have, therefore, been implicated … onstrated with bromodeoxyuridine incorporation, which facilitated axon guidance and subsequent axon remyelination. These results suggest the emergence and proliferation of immature Schwann cells that contribute to nerve regeneration after ischemic injury. The manipulation of this population of proliferating immature Schwann cells may be a useful strategy for tr …

Polysialyltransferase overexpression in Schwann cells mediates different effects during peripheral nerve regeneration.

The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) has been shown to support dynamic changes underlying peripheral nerve regeneration. Using transgenic mice expressing polysialyltransferase ST8SiaIV under control of a glial-specific (proteolipid protein, PLP) promoter (PLP-ST8SiaIV-transgenic mice), we tested the hypothesis that permanent synthesis of PSA in Schwann cells impairs functional recovery of lesioned peripheral nerves. After sciatic nerve crush, histomorphometric analyses demonstrated impaired remyelination of regenerated axons at the lesion site and in tar…

Aberrant upregulation of astroglial ceramide potentiates oligodendrocyte injury.

Oligodendroglial injury is a pathological hallmark of many human white matter diseases, including multiple sclerosis (MS) and periventricula … is. Importantly, this altered sphingolipid metabolism during demyelination was restored upon active remyelination. In culture, ceramide acted synergistically with tumor necrosis factor, leading to apoptotic death of oligodendroglia in an astrocyte-dependent manner. Taken together, our findings implicate that disturbed sphingolipid pathways in reactive astrocyte …

IVIG-pools: regulatory gifts--transiting from harmony toward harmonious immunoglobulins: why? and why not?

Based on 'initial conditions' which depend on each donors' exposure to a unique environment, a pooled intravenous immunoglobulin (IVIG) prod … IG may play minor roles in promoting defense against spontaneous bleeding and, perhaps, stimulating remyelination. The wide spectrum of IVIG specificities, by reflecting evolutionary epitope selection, may not further destabilize cell/molecule disarray in the affected host. Benefit to the patient by IVIG treatment cannot be predicted nor can potentially severe …

Ultrastructural changes in peripheral nerve in hereditary motor and sensory neuropathy-Lom.

Ultrastructural observations have been made on nerve biopsy specimens from five cases of hereditary motor and sensory neuropathy-Lom (HMSNL). A number of features that distinguish it from other hereditary demyelinating neuropathies were identified. Teased fibre studies were not feasible but examination of longitudinal sections by electron microscopy demonstrated demyelination/remyelination. Severe progressive axonal loss was a conspicuous feature. There was no indication of axonal atrophy. Hypertrophic onion bulb changes were present in the younger patients which later regressed, probably seco…

Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis.

The presence of T lymphocytes bearing the gamma delta T-cell receptor (TCR gamma delta) has been studied immunocyto-chemically in central ne … ionships perhaps of significance to the chronicity of the MS disease process and the failure of CNS remyelination.

Cryopreserved Mucosal Olfactory Ensheathing Cells Promote Functional Recovery After Dorsal Root Injury.

Olfactory ensheathing cell (OEC) transplantation has been widely shown to support axonal regeneration, remyelination, and functional recovery after central nervous system injury; however, autologous approaches are limited by low cell yields from patient biopsies, which may be insufficient for large spinal cord lesions. This study evaluated whether cryopreservation could provide a scalable alternative by preserving the therapeutic potential of mucosa-derived OECs. Using a rat dorsal root injury model, cryopreserved mucosa-derived OECs (CmOECs) were thawed and assessed for viability, phenotype, …

Hyaluronic Acid-Based Injectable Dual-Network Hydrogel for 6'-Sialyllactose Mimetic Peptide Delivery and Microenvironment Reconstruction in Brachial Plexus Root Avulsion.

Brachial plexus root avulsion (BPRA) results in extensive motor neurons (MNs) loss, muscle atrophy, and irreversible motor dysfunction. Curr … or function, modulated the local inflammatory microenvironment to preserve the spinal MNs, promoted remyelination of musculocutaneous nerve, attenuated muscle atrophy, offering a promising strategy to restore motor function.

TAK1 Impedes Peripheral Nerve Regeneration After Injury by Evoking Sustained Inflammation.

Peripheral nerve injury (PNI) often leads to severe functional deficits, yet the molecular mechanisms underlying nerve regeneration remain i … ruitment of M1 macrophages and the establishment of a proinflammatory microenvironment that impedes remyelination and nerve regeneration. Collectively, these findings identify TAK1 as a critical negative regulator of peripheral nerve repair and highlight TAK1 inhibition as a potential therapeutic approach for improving recovery following PNI.