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Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.

Neurodegenerative disorders are characterized by progressive neuronal loss and dysfunction, yet increasing evidence indicates that glial cel … s Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis. Recent advances in single-cell and spatial omics have revealed extensive glial heterogeneity and dynamic shifts between neuroprotective and neurotoxic phenotypes, emphasizing the context-dependent nature of glial activity. This review summarizes cu …

Serum HGF and APN2 are associated with disability worsening in SPMS.

There are no reliable biomarkers that predict disability worsening in progressive Multiple Sclerosis (MS). We analyzed circulating biomarkers of hypoxia and angiogenesis in people with Secondary Progressive MS (SPMS) who participated in a clinical trial and were monitored prospectively for disability worsening. Concentrations of glucose transporter-1 (Glut-1), a marker of hypoxia, were higher in SPMS compared to controls. Moreover, low levels of angiopoietin-2 (APN2) and hepatocyte growth factor (HGF) were associated with disability worsening, while neurofilament light, an emerging biomarker i…

Differences in topological progression profile among neurodegenerative diseases from imaging data.

The spatial distribution of atrophy in neurodegenerative diseases suggests that brain connectivity mediates disease propagation. Different d … and individual levels. Experimental results comparing topological profiles for Alzheimer's disease, multiple sclerosis and normal ageing show that topological profiles explain the observed data better than single descriptors. Within each condition, most individual profiles cluster around the cohort-level profile, and individuals whose profiles align more closely wit …

Neuregulin-1 facilitates myelin regeneration through microglia-mediated mechanisms in a mouse model of chronic demyelination.

Impaired myelin repair, or remyelination, is a hallmark of progressive multiple sclerosis (MS) that drives brain degeneration and enduring neurological disabilities. Microglia crucially support remyelination through myelin phagocytosis and lipid metabolism. However, in chronic demyelinated MS lesions, microglia lose their reparative function by acquiring a foamy dysfunctional phenotype characterized by accumulation of lipid droplets due to impaired cholesterol processing of myelin debris. Here, we show a positive correlation between dysregulation of neuregulin-1 and impaired oligodendrocyte re…

Sexual behavior, body image, and partnership in chronic illness: a comparison of Huntington's disease and multiple sclerosis.

Huntington's disease (HD) and multiple sclerosis (MS) are both chronic progressive illnesses posing a serious challenge to affected patients and families. Sexual dysfunction in HD as well as in MS is a very common problem, although it is unclear whether the dysfunction is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness. Twenty-nine patients with HD and 27 patients with MS each participated in a semistructured interview and several standardized questionnaires concerning partnership, sexual function, and body image. The results display significant di…

BTK inhibitors in multiple sclerosis: emerging evidence and future directions.

INTRODUCTION: Available disease modifying treatments (DMTs) for multiple sclerosis (MS) impact on the immune adaptive response without inhibiting innate immune cells that participate in disease progression. Bruton tyrosine kinase (BTK) inhibitors are an emerging treatment being intensely evaluated in MS. This review highlights the potential use of BTK inhibitors in the treatment of MS by exploring mechanisms of action, recent clinical findings, and gaps in implementation. AREAS COVERED: This narrative review traces the roots of the use of BTK inhibitors for the treatment of MS. PubMed, EMBASE…

Neurologic indications for therapeutic plasma exchange: 2013 update.

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review considers the most common neurologic indications for TPE. It focuses on Guillain-Barré syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy. As with any treatment, the proven efficacy, cost, side effects, and availability must be considered be…

Neurologic indications for therapeutic plasma exchange: 2011 update.

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review examines the most common neurologic indications for TPE. It focuses on Guillain-Barre' syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy (PML). As with any treatment, the proven efficacy, cost, side effects, and availability must be conside…

Investigating the role of serum IL-6 in predicting outcomes of b-cell depleting therapy in multiple sclerosis: a retrospective cohort study.

BACKGROUND: Interleukin-6 (IL-6) plays a pivotal role in autoimmune inflammation through its effects on B-cell differentiation, Th17 expansion, and regulatory T-cell suppression. Given ocrelizumab's (OCR) mechanism of selective CD20+ B-cell depletion, baseline IL-6 levels have been hypothesized to predict disease activity and long-term outcomes in multiple sclerosis (MS). However, the prognostic value of serum IL-6 in OCR-treated patients remains unclear. Therefore, the objective of this study was to evaluate whether baseline and longitudinal serum IL-6 levels can predict clinical and radiolog…

[New directions of immunocorrection in multiple sclerosis].

Multiple sclerosis is a central nervous system disease with autoimmune and neurodegenerative mechanisms of development. This disease can lead to severe disability and neurological defects. Although its etiology and pathogenesis remain unclear, research data show that multiple sclerosis is a multifactorial disease, the development of which depends on environmental factors, as well as a genetic predisposition. The impact of these factors lead to the death of neural cells, accompanied by demyelination of nerves and neuronal dysfunction. Therapy of multiple sclerosis is based on the use of anti-in…

Kinetics of serum NFL and GFAP and changes in cognitive functions, in MS patients treated with repeated administrations of autologous mesenchymal stem cells (MSC-NG01).

BACKGROUND: Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (NCT02166021). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial. METHODS: 23 patients with progressive types of MS, who participated in the NCT02166021-trial, were included. Patients we…

Targeting CNS myeloid infiltrates provides neuroprotection in a progressive multiple sclerosis model.

Demyelination and axonal injury in chronic-progressive Multiple Sclerosis (MS) are presumed to be driven by a neurotoxic bystander effect of meningeal-based myeloid infiltrates. There is an unmet clinical need to attenuate disease progression in such forms of CNS-compartmentalized MS. The failure of systemic immune suppressive treatments has highlighted the need for neuroprotective and repair-inducing strategies. Here, we examined whether direct targeting of CNS myeloid cells and modulating their toxicity may prevent irreversible tissue injury in chronic immune-mediated demyelinating disease. …

Gasdermin D activation in oligodendrocytes and microglia drives inflammatory demyelination in progressive multiple sclerosis.

Neuroinflammation coupled with demyelination and neuro-axonal damage in the central nervous system (CNS) contribute to disease advancement in progressive multiple sclerosis (P-MS). Inflammasome activation accompanied by proteolytic cleavage of gasdermin D (GSDMD) results in cellular hyperactivation and lytic death. Using multiple experimental platforms, we investigated the actions of GSDMD within the CNS and its contributions to P-MS. Brain tissues from persons with P-MS showed significantly increased expression of GSDMD, NINJ1, IL-1β, and -18 within chronic active demyelinating lesions compar…

Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.

BACKGROUND: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. METHODS/PRINCIPAL FINDINGS: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluoresc…

Quantification of subtle blood-brain barrier disruption in non-enhancing lesions in multiple sclerosis: a study of disease and lesion subtypes.

Few attempts have been made to detect subtle blood-brain barrier (BBB) leakage in visibly non-enhancing MRI lesions in multiple sclerosis (MS). For 19 patients, longitudinal relaxation time (T1) maps were generated from MRI scans obtained before, and at 20, 40 and 60 minutes after injection of gadolinium (Gd)-DTPA (0.3 mmol/kg). Regions of interest (ROI) were placed around non-enhancing lesions, and in paired contralateral normal appearing brain tissue (NABT). Post-Gd rate of R1 (=1/T1) rise (DeltaR1/Deltat), was used to quantify leakage. DeltaR1/Deltat was greater in lesions than paired NABT …

Idiopathic inflammatory-demyelinating diseases of the central nervous system.

Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a…

Autonomic dysfunctions in multiple sclerosis: Challenges of clinical practice (Review).

Multiple sclerosis, demyelinating, inflammatory, degenerative, and chronic disease, raises many challenges in terms of disease management. The autonomic nervous system is affected by neuroinflammation but also contributes to its maintenance and the evolution of the disease. Multiple sclerosis interfering with parasympathetic or sympathetic modulation may influence the immune response. Less attention is paid to autonomic dysfunctions, although they produce a serious impact on the quality of life. In addition to motor disabilities, patients also have non-motor dysfunctions. Regardless of its cli…

Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives.

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS), are characterized by acute or chronic progressive loss of one or several neuronal subtypes. However, despite their increasing prevalence, little progress has been made in successfully treating these diseases. Research has recently focused on neurotrophic factors (NTFs) as potential regenerative therapy for neurodegenerative diseases. Here, we discuss the current state of knowledge, challe…

Survivor bias and disease progression in observational cohorts in multiple sclerosis.

BACKGROUND: Long-term studies on multiple sclerosis progression often face dropout, possibly among those with more aggressive disease, biasing the cohort. OBJECTIVES: We assessed potential survivorship bias in a long-term observational multiple sclerosis cohort. METHODS: Three hundred sixty-one patients with multiple sclerosis were followed for 10 years, with clinical assessments, blood biomarkers and magnetic resonance imaging at baseline, follow-up 1 and follow-up 2. Progression was defined as an Expanded Disability Status Scale increase. Dropout was analysed and predicted; estimated Expan…

Пентозный фосфатный путь ингибиции метаболизма перепрограммирует CD8+T клетки и нарушает автоиммунитет CNS.

Множественный склероз характеризуется проникновением CNS в автоматически реактивные иммунные клетки, которые приводят как к острому подстрекательскому демиэлированию, так и к хронической прогрессирующей аксонной и нейрональной травме. Расширяющиеся доказательства указывают на то, что CD8+ антиневральные Т клетки в нейродегенерации, которая лежит в основе необратимого клинического прогресса в множественном склерозе, но терапия, конкретно ориентированная на эту клеточную популяцию, ограничена. CD8+T клетки пациентов с MS показывают более активное вовлечение пентоза фосфата. Фармакологическое инг

Совпадение в аннотации оригинала
Multiple sclerosis is characterized by CNS infiltration of autoreactive immune cells that drive both acute inflammatory demyelination and chronic progressive axonal and neuronal injury. Expanding evidence implicates CD8+ antineural T cells in the neurodegeneration that underlies irreversible clinical progression in multiple sclerosis, yet therapies specifica…