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Нацеливание на α7-никотиновый ацетилхолиновый рецептор при множественном склерозе: последствия для иммуномодуляции и нейрозащиты.

Множественный склероз (MS) — хроническое иммунное расстройство, характеризующееся демиелинацией, аксонной дегенерацией и прогрессивной неврологической инвалидностью. Текущие методы лечения с целью изменения заболеваний (ДМТ) неадекватно решают проблемы нейродегенерации и отказа от ремиелинирования, особенно в прогрессивных СМ. α7-никотиновый ацетилхолиновый рецептор (α7-nAChR), являющийся ключевым посредником в холинергическом антивоспалительном пути, стал многообещающей терапевтической целью, которая соединяет иммуномодуляцию и нейрозащиту. Этот обзор синтезирует текущие данные о биологии, ра

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic immune-mediated disorder characterized by demyelination, axonal degeneration, and progressive neurological disability. Current disease-modifying therapies (DMTs) inadequately address neurodegeneration and remyelination failure, particularly in progressive MS. The α7-nicotinic acetylcholine receptor (α7-nAChR), a key media…

[Clinical use of interferon].

It has been thought that there is a particular balance between interferon and humoral immunity in the specific antiviral activity exerted by … tis C and a better knowledge regarding the mechanism of action of beta interferon in the therapy of multiple sclerosis has been acquired. Finally, a remarkable report regards the effectiveness of interferon in the therapy of idiopatic dilated cardiomiopathy.

NLRX1 limits inflammatory neurodegeneration in the anterior visual pathway.

Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple sclerosis (MS). Using multiple experimental autoimmune encephalomyelitis (EAE) models, we discovered that NLRX1 protects neurons in the anterior visual pathway from inflammatory neurodegeneration. We quantified retinal ganglion cell (RGC) density and optic nerve axonal degeneration, gliosis, and T-cell infiltration in Nlrx1-/- and wild-type (WT) EAE mice and found increased RGC loss and axonal injury in Nlrx1-/- mice compared to WT mice in both active immu…

A HIF1A variant impacts long-term disability and smoldering inflammation in multiple sclerosis.

Multiple sclerosis (MS) shows a highly heterogeneous course, with some patients accumulating severe disability early while others remain relatively preserved even after decades. A key driver of disability progression is smoldering inflammation, a chronic, compartmentalized immune process at the edge of chronic active lesions. However, the factors driving smoldering inflammation in MS remain incompletely understood. We investigated the role of genetic variation in smoldering inflammation-related genes across two independent MS cohorts, using a discovery-replication design in a total of 2,817 pa…

Смерть клеток при множественном склерозе.

Множественный склероз (MS) — хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризующееся воспалительным демиэлированием и прогрессивным нейродегенерацией. Несмотря на то, что нынешняя медикаментозная терапия, способствующая изменению заболеваний, является модифицирующей периферическую аутоиммунную реакцию, ее недостаточно для полного предотвращения нейроинфламмации и долгосрочной потери нейронных и олигодендроцитов. Растущие свидетельства указывают на различные регулируемые пути смерти клеток (КОД), включая апоптоз, некроптоз, пироптоз и ферроптоз, не только как

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive neurodegeneration. Although current disease-modifying therapies modulate peripheral autoimmune responses, they are insufficient to fully prevent tissue specific neuroinflammation and long-term neuronal and o…

Demyelination-induced glutamatergic imbalance mediates hippocampal Hyperexcitability.

Chronic demyelination is a hallmark of multiple sclerosis (MS) and is associated with increased seizure susceptibility. In this study, we used the cuprizone (CPZ) diet induced demyelination model to investigate the progression of hippocampal demyelination and its impact on seizure activity and neurotransmitter dysregulation. Using EEG recordings, immunohistochemistry, Western blotting, ELISA, Golgi staining, and NanoString transcriptomics, we found progressive hippocampal demyelination accompanied by a striking increase in seizure incidence, from 38 % at 6 weeks to 88 % by 12 weeks. Structural…

Сокращение ячеек не улучшает восстановления мышей при искусственном обезвоживании аутоиммунной энцефаломиэлитом (EAE).

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся демиэлированием на основе иммунных клеток и прогрессивным нейродегенерацией. В последнее время в хронических поражениях MS наблюдались чувствительные клетки (КЦ), что указывает на их возможное участие в прогрессии заболеваний. Вместе с тем роль СК и потенциальные терапевтические выгоды их сокращения с помощью сенолитной терапии еще предстоит определить в экспериментальной аутоиммунной энцефаломиелите (EAE), широко используемой доклинической модели MS. Здесь мы показываем, чт

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by immune cell-driven demyelination and progressive neurodegeneration. Senescent cells (SCs) have recently been observed in chronic MS lesions indicating their possible involvement in disease progression. However, the role of SCs and the potential ther…

The CD40/CD40 ligand dyad and its downstream effector molecule ISG54 in relating acute neuroinflammation with persistent, progressive demyelination.

Although Multiple Sclerosis (MS) is primarily thought to be an autoimmune condition, its possible viral etiology must be taken into consideration. When mice are administered neurotropic viruses like mouse hepatitis virus MHV-A59, a murine coronavirus, or its isogenic recombinant strain RSA59, neuroinflammation along with demyelination are observed, which are some of the significant manifestations of MS. MHV-A59/RSA59 induced neuroinflammation is one of the best-studied experimental animal models to understand the viral-induced demyelination concurrent with axonal loss. In this experimental ani…

Natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis: a postmortem study.

Natalizumab, a monoclonal antibody directed against α4 integrins, has, to date, been associated with 399 cases of progressive multifocal leukoencephalopathy (PML) worldwide in patients receiving treatment for multiple sclerosis (MS). Because of the limited number of histologic studies, the possible interplay between MS and PML lesions has not been investigated. We report the clinical, radiologic, and histologic findings of an MS patient who developed PML after 32 months of natalizumab monotherapy. After withdrawal of natalizumab, she received plasma exchange, mefloquine, and mirtazapine but di…

Differentially expressed genes in systemic sclerosis: Towards predictive medicine with new molecular tools for clinicians.

Systemic sclerosis (SSc) is a rare and chronic autoimmune disease characterized by a pathogenic triad of immune dysregulation, vasculopathy, and progressive fibrosis. Clinical tools commonly used to assess patients, including the modified Rodnan skin score, difference between limited or diffuse forms of skin involvement, presence of lung, heart or kidney involvement, or of various autoantibodies, are important prognostic factors, but still fail to reflect the large heterogeneity of the disease. SSc treatment options are diverse, ranging from conventional drugs to autologous hematopoietic stem

Brain lesions in chronic granulomatous disease.

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, thr…

Single-cell spatial transcriptomic profiling defines a pathogenic inflammatory niche in chronic active multiple sclerosis lesions.

Compartmentalized inflammation is a key driver of multiple sclerosis (MS) progression, but the mechanisms sustaining its persistence remain unclear. A hallmark of this persistent and slowly evolving inflammatory process is chronic active MS lesions. We generated a high-resolution, single-cell molecular and spatial atlas of such lesions by combining single-nucleus RNA sequencing (snRNA-seq) with multiplexed error-robust fluorescence in situ hybridization (MERFISH). Within lesion rims, we identified CD8+ T cell niches associated with inflamed microglia displaying an interferon response and upreg…

Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CT…

Burrowing of urinary bladder wall by the tip of a size 22 Fr silicone foley catheter in an adult male patient with multiple sclerosis and suprapubic cystostomy: should caution be exercised in using a size 22 Fr silicone foley catheter for long-term drainage of neuropathic bladder?

INTRODUCTION: Silicone Foley catheters tend to become stiffer as size of the catheter increases. Whereas the tip of a size 12 French silicone, Foley catheter is soft and flexible, a size 24 French silicone, Foley catheter is distinctly stiff. Chronically inflamed neuropathic bladders are susceptible to perforation by the tip of a Foley catheter. We report a patient with multiple sclerosis and moderately severe chronic cystitis, in whom a size 22 French Foley catheter burrowed through the dome of urinary bladder. CASE PRESENTATION: A 55-year-old, Caucasian male suffering from multiple sclerosi…

[XVIII Post-ECTRIMS Meeting: Review of the New Developments Presented at the 2025 ECTRIMS Congress (Part II)].

The 18th edition of the post-European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting was held on 17-18 October 2025 in Madrid, bringing together Spanish neurologists specialising in multiple sclerosis (MS), who presented the most relevant advances discussed at the ECTRIMS congress held a few days earlier in Barcelona. The aim of this edition was to present the latest developments in MS regarding the update of diagnostic criteria, advanced neuroimaging techniques, the role of Epstein-Barr virus, remyelination mechanisms and biomarkers. In the therapeutic field, eme…

Major depressive disorder in multiple sclerosis and AQP4-antibody positive neuromyelitis optica spectrum disorder: A cross-sectional study on clinical correlates in Iranian patients.

BACKGROUND: Multiple sclerosis (MS) is a chronic, immune-mediated neuroinflammatory disorder of the central nervous system (CNS). Symptoms of depression are more prevalent among patients with MS (PwMS) compared to both the general population and individuals with other chronic debilitating conditions. OBJECTIVES: This cross-sectional study aimed to examine the prevalence of major depressive disorder (MDD) in PwMS across different MS subtypes, as well as in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD). Also, it sought to identify various risk factors associated with MDD in these…

Multiple sclerosis: immune mechanism and update on current therapies.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third of MS patients have chronic progressive disease often leading to severe impairment of mobility, paralysis, poor vision, and disturbances of bladder and bowel function. Although the etiology and pathogenesis remain unknown, accumulating evidence supports the hypothesis that exposure…

Recommended outcome measures for inpatient rehabilitation of multiple sclerosis are not appropriate for the patients with substantially impaired mobility.

BACKGROUND: In multiple sclerosis (MS) rehabilitation, most currently used outcome measures were validated in patients with a relapsing remitting MS and mild to moderate impairments. We aimed to assess whether these measures were also adequate in more impaired patients, frequently encountered in those with progressive MS (PMS). METHODS: Outcome measurements were extracted from medical records of 229 patients with PMS undergoing 3 weeks of routine inpatient rehabilitation between 2011 and 2015. We assessed the acceptability of Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW), 2-Minute Wal…

Fast multiple sclerosis progression in North Africans: Both genetics and environment matter.

OBJECTIVE: To compare multiple sclerosis (MS) disability progression among North Africans (NAs) living in France (NAF) and in Tunisia (NAT) and Caucasian patients born and living in France (CF). METHODS: Patients with MS admitted to the day hospital in the Neurology Department at Pitié-Salpêtrière Hospital (France) and Razi Hospital (Tunisia) were questioned on their place of birth and the place of birth of their parents. To compare delay to outcomes, log-rank tests were used. Univariate and multivariate Cox models were used to determine factors influencing time to Expanded Disability Status …

[MRI comparison between hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and primary progressive multiple sclerosis (PPMS)].

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant inherited leukoencephalopathy characterized by … r, in some cases, when motor symptoms precede cognitive decline, HDLS may mimic primary progressive multiple sclerosis (PPMS). Herein we tried to clarify MRI features of HDLS (2 women, age 22-28 years, average 25.0 years, EDSS 7.00) in comparison with PPMS (6 men and 10 women, age 29-64 years, average 33.7 years, EDSS 6.03). In consequence, our MRI findings suggesti …