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miR-146a is a Pleiotropic Regulator of Motor Neuron Degeneration.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Here, we have profiled motor neuron microRNAs (miRNAs) during motor neuron degeneration in vivo to gain a better understanding of ALS pathophysiology. We demonstrate that one miRNA, miR-146a, is downregulated in diseased motor neurons despite upregulation in bulk tissue. Genetic deletion of miR-146a significantly extended survival in SOD1G93A mice with heterozygous animals demonstrating the largest benefit. A corresponding reduction in spinal cord gliosis but not motor neuron loss was observ

Mitochondrial Dysfunction and Multiple Sclerosis.

In recent years, several studies have examined the potential associations between mitochondrial dysfunction and neurodegenerative diseases such as multiple sclerosis (MS), Parkinson's disease and Alzheimer's disease. In MS, neurological disability results from inflammation, demyelination, and ultimately, axonal damage within the central nervous system. The sustained inflammatory phase of the disease leads to ion channel changes and chronic oxidative stress. Several independent investigations have demonstrated mitochondrial respiratory chain deficiency in MS, as well as abnormalities in mitocho…

[B-cell Therapy for Multiple Sclerosis].

B-cell therapy using anti-CD20 antibodies significantly suppresses relapse and is therefore an important treatment option for multiple sclerosis (MS). Based on the production of inflammatory cytokines and enhanced antigen-presenting capacity, B cells trigger MS relapses via activation of pathogenic T cells. Suppression of these abnormal actions of B cells is the primary mechanism underlying relapse prevention using B-cell therapies. Treatments that target B cells are also expected to suppress chronic progression of MS through modulation of B-cell activity within the central nervous system. B-c…

Informing patients with progressive neurological disease of their health status, and their adaptation to the disease.

BACKGROUND: Progressive neurological diseases, such as multiple sclerosis, Parkinson's disease, Huntington's disease, significantly interfere with patients' lives, and those of their families. The aim of the research was to establish whether the extent of the information on patients' health conditions, and the way patients learn this information from doctors affect their adaptation to chronic and progressive diseases. METHODS: Qualitative methodology was used for a total of 52 participants (patients with progressive neurological diseases, their family members, and health and social workers). …

Ассоциация " Myokines " , " Инфламация " и " Состояние питания пациентов с множественным склерозом " .

Последние исследования свидетельствуют о том, что при прогрессивном множественном склерозе (MS) - воспалительном и дегенеративном заболевании центральной нервной системы - биологические пути, связанные с этим воздействием, остаются недостаточно понятными. Изменения в весе тела, будь то избыточный вес или недостаточный вес, а также изменения в жире и мышечной ткани, наряду с хроническим воспалением, могут способствовать болезни и влиять на ее ход.ЦЕЛЬ: Это тематическое исследование было направлено на измерение подстрекательских маркеров и уровней миокина (миостатина и ирисина), нейротрофическог

Совпадение в аннотации оригинала
BACKGROUND: Recent studies indicate that in progressive multiple sclerosis (MS)-an inflammatory and degenerative disease of the central nervous system-the biological pathways associated with these effects remain poorly understood. Changes in body weight, whether presenting as overweight or underweight, as well as alterations in adipose and muscle tissue, tog…

Spatially-restricted inflammation-induced senescent-like glia in multiple sclerosis and patient-derived organoids.

In multiple sclerosis (MS), chronic compartmentalized inflammation is thought to drive relentless clinical deterioration. Here, we investigate the link between unresolved parenchymal inflammation and cellular senescence in MS progression. Single-cell transcriptomic analysis of human brain tissue reveals an accumulation of senescent-like glial cells in diseased white matter, especially in chronic active lesions, and to a lesser extent in the cortex. Spatial transcriptomics show gradients of senescence-like signatures extending from lesion cores to periplaque regions, alongside rewired cellular …

Neurodegenerative Diseases: Can Caffeine Be a Powerful Ally to Weaken Neuroinflammation?

In recent years, there has been considerable research showing that coffee consumption seems to be beneficial to human health, as it contains … . The most known chronic NDs are represented by Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). According to epidemiological studies, regular coffee consumption is associated with a lower risk of neurodegenerative diseases. In this review, we summarize the latest research …

Looking Beyond Dose: Identifying Responders and Non-Responders to RehaCom Computerized Cognitive Rehabilitation in Progressive MS-The CogEx Study.

BackgroundRehaCom, a computerized cognitive rehabilitation program for people with multiple sclerosis (PwMS), has been studied primarily in relation to treatment "dose" (duration, frequency, and adherence), with less focus on which training modules drive improvement or which participant factors predict responsiveness. This secondary analysis of the CogEx trial investigated whether progression within specific RehaCom modules was associated with processing speed improvement, measured by the SDMT, and whether baseline characteristics predicted response in participants with progressive MS.MethodsA…

Effect of repurposed simvastatin on disability progression in secondary progressive multiple sclerosis (MS-STAT2): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Despite the success of immune modulation in the treatment of relapsing multiple sclerosis, disability progression is a major problem driven by multiple mechanisms. Comorbidities (eg, vascular risk) and ageing are thought to augment these neurodegenerative pathologies. In the phase 2b MS-STAT trial of simvastatin (80 mg) versus placebo in secondary progressive multiple sclerosis (SPMS), the adjusted difference in brain atrophy rate between groups was -0·254% per year: a 43% reduction. In this phase 3 MS-STAT2 trial, we aimed to assess the efficacy of simvastatin versus placebo in sl…

Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial.

BACKGROUND: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS). METHODS: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks. We measured peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses. Statistical analysis included correlati…

Microglial suppression by myeloperoxidase inhibitor does not delay neurodegeneration in a mouse model of progressive multiple sclerosis.

Drugs able to efficiently counteract the progression of multiple sclerosis (MS) are still an unmet need. Numerous preclinical evidence indicates that reactive oxygen-generating enzyme myeloperoxidase (MPO), expressed by neutrophils and microglia, might play a key role in neurodegenerative disorders. Then, the MPO inhibition has been evaluated in clinical trials in Parkinson's and multiple system atrophy patients, and a clinical trial for the treatment of amyotrophic lateral sclerosis is underway. The effects of MPO inhibition on MS patients have not yet been explored. In the present study, by …

The ABILHAND-23 Patient Reported Outcome Measure in Secondary Progressive Multiple Sclerosis: A Cross-Sectional Analysis With the Nine Hole Peg Test.

BACKGROUND: People with progressive multiple sclerosis (pwPMS), who typically have established lower limb dysfunction, experience greater disability from upper limb dysfunction (ULD). The 9-hole peg test (9HPT) is the primary clinical measure for ULD but does not fully capture the patient experience. The ABILHAND-23 is a well-validated patient-reported outcome measure (PROM) that evaluates bimanual ability in daily function. However, no large-scale studies have assessed if the 9HPT reflects the individual ULD experience in pwPMS. OBJECTIVES: We sought to (van Munster et al. 2023) assess the a…

Synthetic MRI in Progressive MS: Associations with Disability.

BACKGROUND AND PURPOSE: Synthetic MRI (SyMRI) is a short-time acquisition sequence that generates different contrast-weighted images based on the measurement of tissue properties and provides quantitative volumetric, relaxation, and myelin maps. It has been used as an alternative to conventional MRI sequences in relapsing-remitting MS for detecting focal lesions and volumetric analysis. This study aimed to find an SyMRI variable associated with an Expanded Disability Status Scale (EDSS) ≥ 6 in progressive patients. MATERIALS AND METHODS: Twenty-four patients with progressive MS underwent SyMR

Siponimod ameliorates metabolic oligodendrocyte injury via the sphingosine-1 phosphate receptor 5.

Multiple sclerosis (MS), an autoimmune-driven, inflammatory demyelinating disease of the central nervous system (CNS), causes irreversible accumulation of neurological deficits to a variable extent. Although there are potent disease-modifying agents for its initial relapsing-remitting phase, immunosuppressive therapies show limited efficacy in secondary progressive MS (SPMS). Although modulation of sphingosine-1 phosphate receptors has proven beneficial during SPMS, the underlying mechanisms are poorly understood. In this project, we followed the hypothesis that siponimod, a sphingosine-1 phos…

Autonomic nervous system abnormalities predict cardiovascular changes after initiation of siponimod in secondary progressive multiple sclerosis.

OBJECTIVE: The aim of this study was to identify whether autonomic nervous system (ANS) dysfunction identified prior to treatment initiation can predict siponimod related decrease in heart rate (HR) after treatment initiation. METHODS: In 26 people with secondary progressive multiple sclerosis (SPMS) the following ANS testing protocol was applied: 10-min supine resting position, Valsalva maneuver, deep breathing test, 10 min tilt-up table test, 5-min supine resting period, ingestion of siponimod, followed by 180-min supine resting period recordings. Heart rate variability (HRV) parameters wer…

Anti-CD20 Disrupts Meningeal B-Cell Aggregates in a Model of Secondary Progressive Multiple Sclerosis.

OBJECTIVE: Therapies targeting B cells have been used in the clinic for multiple sclerosis (MS). In patients with relapsing MS, anti-CD20 therapy often suppresses relapse activity; yet, their effect on disease progression has been disappointing. Most anti-CD20 therapeutic antibodies are type I, but within the unique microenvironment of the brain, type II antibodies may be more beneficial, as type II antibodies exhibit reduced complement-dependent cytotoxicity and they have an increased capacity to induce direct cell death that is independent of the host immune response. METHODS: We compared t…

[11C]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [11C]PIB is widely used for detection of β-amyloid plaques, but has also been suggested for the analysis of myelin content …

Influence of Peripheral inflammation on the progression of multiple sclerosis: evidence from the clinic and experimental animal models.

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination, remyelination and loss of functions. Even though its etiology is unknown viral, genetic and environmental factors are considered triggers of the disease. MS shows a heterogeneous clinical course, but most patients exhibit exacerbations and remissions from the onset, eventually leading to secondary progressive multiple sclerosis. Systemic inflammatory events are known to signal into the central nervous system (CNS), and can induce a general response known as sickness behavior. Several research papers have …

Hirayama Disease Presenting as 4-Limb Paresthesia.

INTRODUCTION: Hirayama disease is a rare clinical entity that presents typically as a unilateral, slowly progressive arms weakness, mostly o … cord atrophy. Involvement of all 4 limbs is rare, and the condition can be mistaken for progressive multiple sclerosis.

Microglia pre-activation and neurodegeneration precipitate neuroinflammation without exacerbating tissue injury in experimental autoimmune encephalomyelitis.

Human inflammatory or neurodegenerative diseases, such as progressive multiple sclerosis (MS), occur on a background of age-related microglia activation and iron accumulation as well as pre-existing neurodegeneration. Most experimental models for CNS diseases, however, are induced in rodents, which are naturally characterized by a homeostatic microglia phenotype, low cellular iron load and absence of neurodegeneration. Here, we show that naïve LEWzizi rats - Lewis rats with a zitter rat background - show a spontaneous phenotype partly mimicking the changes seen in human aging and particularly …