Progressive multiple sclerosis: from pathophysiology to therapeutic strategies

Faissner, Simon; Plemel, Jason R.; Gold, Ralf; Yong, V. Wee

doi:10.1038/s41573-019-0035-2

Cited by 344 publications

(294 citation statements)

References 179 publications

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“…Approximately 40-60% of MS patients develop cognitive impairments, affecting memory, executive function, and processing speed [82,83]. Inflammation, demyelination, mitochondrial dysfunction, and axonal loss are the main pathophysiological hallmarks of MS [84,85].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Cheon

Kim

et al. 2020

IJMS

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Cognitive symptoms are prevalent in the elderly and are associated with an elevated risk of developing dementia. Disease-driven changes can cause cognitive disabilities in memory, attention, and language. The inflammasome is an innate immune intracellular complex that has a critical role in the host defense system, in that it senses infectious pathogen-associated and endogenous danger-associated molecular patterns. An unbalanced or dysregulated inflammasome is associated with infectious, inflammatory, and neurodegenerative diseases. Due to its importance in such pathological conditions, the inflammasome is an emerging drug target for human diseases. A growing number of studies have revealed links between cognitive symptoms and the inflammasome. Several studies have shown that reducing the inflammasome component mitigates cognitive symptoms in diseased states. Therefore, understanding the inflammasome regulatory mechanisms may be required for the prevention and treatment of cognitive symptoms. The purpose of this review is to discuss the current understanding of the inflammasome and its relationships with cognitive symptoms in various human diseases.

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Section: Multiple Sclerosismentioning

confidence: 99%

Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Cheon

Kim

et al. 2020

IJMS

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“…Acid Die zugrunde liegenden Ursachen sind mannigfaltig und umfassen ▪ chronische Inflammation hinter einer relativ geschlossenen Blut-Hirn-Schranke, ▪ Aktivierung von Mikroglia, ▪ oxidativen Stress, ▪ Bildung von follikelartigen B-Zell-Strukturen und ▪ altersabhängige Akkumulation von Eisen [1,2].…”

Section: Appunclassified

Neue Therapieansätze bei progredienter Multipler Sklerose

Faissner¹,

Gold²

2020

Neuroradiol Scan

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“…Apart from the above-mentioned therapeutics, there is a plethora of substances and treatment strategies that might potentially be effective due to positive effects in culture or animal models, reviewed elsewhere by the authors. 54 A large screening of potentially remyelinating therapies showed that antimuscarinergic medications, especially clemastine, might be effective in promoting remyelination. 35 Since iron-mediated neurotoxicity is another feature driving progression, we performed a screening to find protective generic medications.…”

Section: Neuroprotective and Experimental Approachesmentioning

confidence: 99%

Progressive multiple sclerosis: latest therapeutic developments and future directions

Faissner

Gold

2019

Ther Adv Neurol Disord

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Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system leading to demyelination and neurodegeneration. While the initial presentation is mostly characterized by a relapsing–remitting disease, patients often progress naturally after 10–15 years to a secondary-progressive disease course. Another 10–15% present with an initial, primary-progressive MS course. Pathogenic mechanisms possibly driving progression include continued compartmentalized inflammation by T- and B-lymphocytes and cells of innate immunity, oxidative stress, iron accumulation, and consecutive mitochondrial damage, altogether leading to neurodegeneration with accumulation of disability. Increasing knowledge about pathogenic mechanisms involved in progressive MS helps to design more specific and precise therapeutic approaches. Successful examples are the B-cell targeting monoclonal antibody ocrelizumab, effective in primary progressive MS, and the sphingosine-1-receptor modulator siponimod, effective in active forms of secondary-progressive MS. Apart from that, other medications such as the B-cell targeted antibody ofatumumab, cladribine due to T- and B-cell depletion, and other sphingosine-1-receptor modulators such as ozanimod and ponesimod are under development. Moreover, some therapeutic approaches in preclinical stages are under development. In this review, we will summarize the newest therapeutic development in the field of progressive MS of the last 3 years, and shed light on auspicious substances with similar mechanisms and new developments in the therapeutic pipeline, presumably supporting a bright future for progressive MS treatment.

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Progressive multiple sclerosis: from pathophysiology to therapeutic strategies

Cited by 344 publications

References 179 publications

Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Neue Therapieansätze bei progredienter Multipler Sklerose

Progressive multiple sclerosis: latest therapeutic developments and future directions

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