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The Role of the Inflammasome in Neurodegenerative Diseases.

Neurodegenerative diseases are chronic, progressive disorders that occur in the central nervous system (CNS). They are characterized by the loss of neuronal structure and function and are associated with inflammation. Inflammation of the CNS is called neuroinflammation, which has been implicated in most neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Much evidence indicates that these different conditions share a common inflammatory mechanism: the activation of the inflammasome complex in…

Молекулярная Интерплей ISG15/ISGILation in Neuropathologies.

ISG15 — белок, похожий на 15 кДа, который кавалентно связывается с его целевыми белками посредством последовательного энзиматического процесса, известного как ISGILation. В последние годы активизировались исследования в области белковой ИГСИЭ, и некоторые исследования показали, что ИГС15 участвует в механизмах нейрозащиты и нейродегенерации. В настоящем обзоре описывается нынешнее состояние исследований по вопросу о последствиях ISG15/ISGilation в других нейропатиях, таких, как злокачественные опухоли, атаксия Телангиэктазия, ишемия, депрессия и нейродегенеративные заболевания, такие, как боле

Совпадение в аннотации оригинала
ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGy … ia, ischemia, depression, and neurodegenerative diseases such as Alzheimer's, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neurop …

Clemastine fumarate promotes myelin repair in a nonhuman primate model of demyelination characterized by absent spontaneous remyelination.

Promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery in white matter diseases such as multiple sclerosis. Clemastine fumarate among several promyelinating agents, has been validated as a promyelinating agent in rodents and has led to a first successful double-blind, placebo-controlled clinical trial evaluating a remyelinating therapy for multiple sclerosis (MS) [A. J. Green et al., Lancet 390, 2481-2489 (2017)]. To date, most of promyelinating strategies have been developed in short-lived rodent models of demyelination, which spo…

Множественные обновления склероза и безопасность и эффективность ингибиторов брютона тиросина киназы: систематический обзор.

Множественный склероз (MS) — хроническое нервно-дегенеративное и аутоиммунное заболевание, характеризующееся воспалением и обезвоживанием CNS. Несмотря на то, что нынешняя медикаментозная терапия (ДМТ) может уменьшить периферическую иммунную реакцию, ее воздействие на кадрализованное воспаление CNS остается ограниченным. В качестве перспективных пероральных агентов, направленных как на клетки B, так и на микроглию, появились ингибиторы Bruton Tyrosine Kinase (BTKis). ЦЕЛЬ: Оценка характеристик безопасности и эффективности двух ингибиторов BTK - Tolebrutinib и Evobrutinib - в борьбе с повторным

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease characterized by CNS inflammation and demyelination. Although current disease-modifying therapies (DMTs) can reduce peripheral immune responses, their impact on CNS-compartmentalized inflammation remains limited. Bruton Tyrosine Kinase inhibitors (BTKis) have emerged as…

Focal amyotrophy in multiple sclerosis.

INTRODUCTION: The assumption that multiple sclerosis (MS) is purely a white matter disease has been challenged in recent years by observations of axonal damage and neuronal loss in gray matter of the cortex, subcortex, and spinal cord. METHODS: We report the case of a 71-year-old man with primary progressive MS and longstanding right arm weakness who presented with intermittent right arm pain. RESULTS: Neurological examination showed atrophy, weakness, and hyporeflexia, and electromyography (EMG) showed acute and chronic partial denervation in multiple segments of the right arm. Magnetic res…

Interventions to Improve Quality of Life in Multiple Sclerosis: New Opportunities and Key Talking Points.

BACKGROUND: Today, living well with multiple sclerosis (MS) is often measured by a person's overall quality of life rather than being limited to the more traditional metrics of reduced frequency of relapses or progression of disability. This change in focus, to a more holistic view of health, such as overall quality of life, has shifted the views of what both providers and people with multiple sclerosis view as essential for living well with MS. PURPOSE: This narrative review aims to examine the relevant literature on existing and emerging non-pharmacological interventions shown to improve th…

Oxidative stress induced by lipid peroxidation is related with inflammation of demyelination and neurodegeneration in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune demyelination disorder of the central nervous system (CNS) and its etiology remains unknown. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines, which contribute to the development and progression of multiple sclerosis. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress is involved in the inflammation leading demyelination and neurodegeneration in the pathogenesis of multiple sclerosis. SUMMARY: The pres…

The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell pop … lex bidirectional roles of the cGAS-STING pathway in Alzheimer's disease, Huntington's disease, and multiple sclerosis, revealing their double-edged nature in disease progression. The objective of this review is to elucidate the pivotal role of the cGAS-STING pathway in ND pathogenesis and catalyze new insights for facilitating the development of novel therapeutic s …

TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood.

BACKGROUND: T cells play a key role in the pathogenesis of multiple sclerosis (MS), a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Although several studies recently investigated the T-cell receptor (TCR) repertoire in cerebrospinal fluid (CSF) of MS patients by high-throughput sequencing (HTS), a deep analysis on repertoire similarities and differences among compartments is still missing. METHODS: We performed comprehensive bioinformatics on high-dimensional TCR Vβ sequencing data from published and unpublished MS and healthy donors (HD) studies. We evalua…

The course of early-onset multiple sclerosis in Iraqi children.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system that is increasingly recognized worldwide in children and adolescents. The current study aimed at identifying the clinical characteristics of MS with onset under 18 years of age. METHODS: This cross-sectional study was conducted in the Multiple Sclerosis Center archive system in Baghdad Teaching Hospital during the period from March 1 to May 15, 2008. The records of 1125 MS patients from 2000 to 2008 were reviewed. Among them 77 patients had the onset of MS under 18 years of age. RESULTS: Two…

Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis.

Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood-brain barrier endothelium, in lesional and normal-appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS. Immunocytochemistry and semiquantitative confocal microscopy for the t…

Autoimmune hepatitis with multiple sclerosis and graves disease: coincidence or association?

Autoimmune hepatitis (AIH) is a generally progressive, chronic hepatitis of unknown cause that occurs in children and adults of all ages. It is associated with a variety of autoimmune conditions like thyroid disorders (Hashimoto and Graves disease), celiac disease and multiple sclerosis (MS). We report the case of a 61-year-old woman with MS (untreated) and a history of Graves disease who presented with fatigue and right upper quadrant abdominal pain. She was admitted to our hospital for evaluation. Clinical and laboratory workup revealed AIH. She was successfully treated with prednisone and a…

Systemic Sclerosis Presenting with Simultaneous Retinal Vasculitis in One Eye and Optic Neuritis in the other along with Severe Immune Haemolytic Anaemia.

Systemic Sclerosis (SSc) is a connective tissue disorder which involves multiple systems in a chronic progressive manner. Micro-angiopathic haemolytic anaemia is a distinguished feature of "scleroderma renal crisis", which is manifested by severe hypertension, a rapidly progressing renal dysfunction and hyperreninaemia and is seen in patients with an early, diffuse form of the disease. A nervous system involvement is rare, though entrapment neuropathies have been reported. Who presented with a sequential loss of vision in both eyes; due to retinal vasculitis in right eye and optic nerve demyel

Взрослые и дети имеют статус координатора по вопросам эпилепсии и эпилепсии continua.

Эпилептический эпилептический и эпилепсиа particentis continua (FSE-EPC) наиболее часто встречается с хроническим хроническим прогрессивным энцефалитом Расмуссена и русским весенним энцефалитом. FSE-EPC, возможно, является характерной особенностью некетотического гипергликемического сахарного диабета, но чаще всего его называют поздним осложнением, особенно если имеет место сопутствующее церебральное повреждение, например церебральное инфаркт. FSE-EPC может быть связан с множественным склерозом, первичными или метастатическими опухолями мозга, синдромом МЕРРФ-МЕЛАС, доброкачественной эпилепсие

Совпадение в аннотации оригинала
Focal status epilepticus and epilepsia partialis continua (FSE-EPC) are most frequently seen with chronic focal progressive encephalitis of … lly if there is a coexistent cerebral lesion such as cerebral infarction. FSE-EPC may be related to multiple sclerosis, primary or metastatic brain tumors, the MERRF-MELAS syndrome, benign epilepsy of childhood with rolandic spikes, and in some adults with acquired aphasia. The physiological origin of the myoclonic jerks seen in EPC is cortical and may be either spo …

[Further experiences with the Imurek treatment in multiple sclerosis].

A report is given on 82 patients suffering from multiple sclerosis (MS) who were treated over a period of up to a maximum of eight years - average treatment 4-6 years. The best results were found in patients passing through an acute episode. Among the chronic-progressive cases, 5.1 per cent of the patients showed an improvement. In 24.4 per cent of the cases the clinical picture remained unchanged. 64.1 per cent showed a deterioration. Side-effects were gastric complaints, considerable leucocyte depression, oedemas, loss of hair, strumata, increase in transaminases, recrudescence of mycosis an…

Why are some people with neurological illness more resilient than others?

The current qualitative study was designed to evaluate the coping strategies of people living with a chronic progressive neurological illness and their carers. The neurological illnesses were Huntington's disease, motor neurone disease, multiple sclerosis and Parkinson's disease. Participants included 15 people who showed high levels of adjustment and 15 who showed low levels of adjustment. Participants were selected from an earlier study, to ensure that they satisfied the inclusion criteria for the current study. Interviews were completed to determine the strategies used to cope with the dema…

Brain region dependent molecular signatures and myelin repair following chronic demyelination.

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyeli…

A friend in need may not be a friend indeed: role of microglia in neurodegenerative diseases.

Inflammation plays a critical role in the progression of neurodegenerative diseases. Microglia are the resident macrophages of the central nervous system (CNS) which actively take part in the neuronal development of CNS and are involved in clearance of pathogens as well as cellular debris from the system upon insult to this organization. Chronic activation of microglia in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) as well as inflammatory conditions of CNS such as multiple sclerosis (MS) …

Parry-Romberg Syndrome with Uhthoff's Phenomena: A Spectrum of Autoimmune Disease?

Parry-Romberg syndrome (PRS) is a rare disorder characterized by unilateral facial atrophy. Currently, the pathogenesis of PRS is poorly und … ted. The present case suggests that PRS may possibly have an autoimmune etiology resembling that of multiple sclerosis.

A 71-year-old male with 4 decades of symptoms referable to both central and peripheral nervous system.

May 2005. Combined demyelination of the central and peripheral nervous system is an uncommon disorder and has been referred to by many appellations. We present the case of a 71-year-old man with a progressive nervous system disorder beginning in his 30s. The diagnosis in life was unclear, but had over the years been variously considered to be Guillain-Barrè Syndrome (GBS), Friedreich ataxia, or multiple sclerosis (MS). At autopsy old CNS demyelination consistent with MS was found as well as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with onion bulb formation in hypertroph…