Dataset Information

Re-Examining the Role of TNF in MS Pathogenesis and Therapy.

ABSTRACT: Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.

SUBMITTER: Fresegna D

PROVIDER: S-EPMC7602209 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Re-Examining the Role of TNF in MS Pathogenesis and Therapy.

Fresegna Diego D Bullitta Silvia S Musella Alessandra A Rizzo Francesca Romana FR De Vito Francesca F Guadalupi Livia L Caioli Silvia S Balletta Sara S Sanna Krizia K Dolcetti Ettore E Vanni Valentina V Bruno Antonio A Buttari Fabio F Stampanoni Bassi Mario M Mandolesi Georgia G Centonze Diego D Gentile Antonietta A

Cells 20201014 10

Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human ...[more]

PMID: 33066433

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Project description:Substantial progress has been made in the medical management of rheumatoid arthritis (RA) over the past decade with the introduction of biologic therapies, including anti-tumour necrosis factor alpha (anti-TNF?) therapy medications. However, individuals with RA taking anti-TNF? medication continue to experience physical, psychological and functional consequences, which could potentially benefit from rehabilitation. There is evidence that therapeutic exercise should be included as an intervention for people with RA, but to date there is little evidence of the benefits of therapeutic exercise for people with RA on anti-TNF? therapy medication. A protocol for a multicentre randomised controlled three-armed study which aims to examine the effect of dynamic group exercise therapy on land or in water for people with RA taking anti-TNF? therapy medication is described.Six hundred and eighteen individuals with RA, on anti-TNF? therapy medication, will be randomised into one of 3 groups: a land-based exercise group; a water-based exercise group or a control group. The land and water-based groups will exercise for one hour, twice a week for eight weeks. The control group will receive no intervention and will be asked not to alter their exercise habits for the duration of the study. The primary outcome measure, the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) which measures functional ability, and secondary measures of pain, fatigue and quality of life, will be assessed at baseline, eight and 24 weeks by an independent assessor unaware of group allocation. Changes in outcome from 0 to 8 weeks and 0 to 24 weeks in the 'land-based exercise group versus control group' and the 'water-based exercise group versus control group' will be examined. Analysis will be conducted on an intention to treat basis.This trial will evaluate the effectiveness of group exercise therapy on land or in water, for people with RA taking anti-TNF? therapy medication. If these exercise groups are found to be beneficial, they could be conducted in local community facilities thus making these forms of exercise more easily accessible for individuals and potentially reduce the burden on health services.This trial is registered with ClinicalTrials.gov (a service of the United States National Institutes of Health) identifier: NCT00855322.

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Re-Examining the Role of TNF in MS Pathogenesis and Therapy.

Publications

Re-Examining the Role of TNF in MS Pathogenesis and Therapy.

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