The role of inflammasomes in multiple sclerosis

2020 ◽  
pp. 135245852093277
Author(s):  
Hanie Yavarpour-Bali ◽  
Maryam Ghasemi-Kasman
Keyword(s):  
Multiple Sclerosis ◽  
Protein Complexes ◽  
Critical Role ◽  
Immunosuppressive Drugs ◽  
Inflammasome Activation ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Current Therapies ◽  
The Central Nervous System ◽  
Inflammatory Autoimmune Disease

Multiple sclerosis (MS) is considered as an inflammatory autoimmune disease of the central nervous system (CNS), with a complex and heterogenic etiology. However, the involvement of inflammation in its pathophysiology is well documented and current therapies for MS are mainly immunosuppressive drugs. Although the available drugs reduce new lesions and relapses, their long-term outcome is not completely satisfactory. Inflammasomes are multimeric protein complexes that play a critical role in the inflammatory process. Several lines of evidence suggest an association between inflammasome activation and MS. In this paper, we have reviewed current studies that demonstrate the involvement of inflammasomes in MS development, in both animal model and MS patients. Furthermore, prior studies about the effect of inflammasome inhibitor drugs on development and progression of MS are discussed.

Recent advances on immunosuppressive drugs and remyelination enhancers for the treatment of multiple sclerosis

2021 ◽  
Vol 27 ◽  
Author(s):  
Jennifer Cadenas-Fernández ◽  
Pablo Ahumada-Pascual ◽  
Luis Sanz Andreu ◽  
Ana Velasco
Keyword(s):  
Multiple Sclerosis ◽  
Intracellular Signaling ◽  
Demyelinating Disease ◽  
Lipid Synthesis ◽  
Immunosuppressive Drugs ◽  
Nerve Fibers ◽  
Myelin Sheaths ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Lipid Structures

: Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures which are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in the MS research is to find treatments which allows the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and whose use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies which have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as, “myelin sheath”, “remyelination”, “demyelination”, “oligodendrocyte” and “lipid synthesis” were used to focus the search. We favoured papers published after January, 2015, but did not exclude earlier seminal papers.

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

scholarly journals PECULIARITIES OF THE CLINICAL COURSE OF POSTMEASLES ENCEPHALITIS IN IMMUNOSUPRESSED PEOPLE

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Tetiana Nehrych ◽  
◽  
Maria Shorobura ◽  
Irina Hritsyna ◽  
Liliia Yukhimiv ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Inclusion Body ◽  
Bacterial Pneumonia ◽  
Clinical Course ◽  
Risk Group ◽  
Neurological Complications ◽  
Immunosuppressive Drugs ◽  
The Central Nervous System ◽  
The Brain

Primary acute measles encephalitis and acute postmeasles encephalitis are the most common neurological complications of measles. It is important to detect encephalitis, which develops a month or more after the manifestations of measles infection. These encephalitis are rare and occur mainly in people with immunodefi ciency. Multiple sclerosis is a chronic disease of the central nervous system for the treatment of which diseasemodifying therapy is used, namely monoclonal antibodies, that can lead to immunosuppression and immunodefi ciency. Nowadays, there is insuffi cient information about the course of postcortical encephalitis in patients with multiple sclerosis who are taking immunosuppressive drugs. The article presents data on the clinical classifi cation, diagnosis and treatment of measles encephalitis. A clinical case of measles inclusion body encephalitis in a thirty-threeyear-old patient with multiple sclerosis on the background of annual intake of monoclonal antibodies is presented. She also had viral-bacterial pneumonia and developed disseminated intravascular coagulation in the brain and lungs. These complications of measles infection led to the death of the person after a month and a half of intensive care. Thus, patients with multiple sclerosis who are taking drugs with immunosuppressive eff ects are among the risk group for measles inclusion body encephalitis. Measles inclusion body encephalitis in such patients can be severe, which complicates timely diagnosis, proper treatment and leads to death.

Relapse rates and long-term outcome in primary angiitis of the central nervous system

2019 ◽  
Vol 266 (6) ◽  
pp. 1481-1489 ◽  
Author(s):  
Simon Schuster ◽  
Ann-Kathrin Ozga ◽  
Jan-Patrick Stellmann ◽  
Milani Deb-Chatterji ◽  
Vivien Häußler ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Primary Angiitis ◽  
The Central Nervous System ◽  
Relapse Rates

Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta

2013 ◽  
Vol 73 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Robert A. Bermel ◽  
Xiaojun You ◽  
Pamela Foulds ◽  
Robert Hyde ◽  
Jack H. Simon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Multiple Sclerosis Patients

Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis

2016 ◽  
Vol 37 (7) ◽  
pp. 1113-1117 ◽  
Author(s):  
Rocco Totaro ◽  
C. Di Carmine ◽  
A. Splendiani ◽  
S. Torlone ◽  
L. Patriarca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Demyelinating Lesions

scholarly journals A Novel Mutation c.841C>T in COPA Syndrome of an 11-Year-Old Boy: A Case Report and Short Literature Review

2021 ◽  
Vol 9 ◽  
Author(s):  
Jingxia Zeng ◽  
Jing Hao ◽  
Wei Zhou ◽  
Zhaoqun Zhou ◽  
Hongjun Miao
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Retrograde Transport ◽  
Immunosuppressive Drugs ◽  
Kidney Disorder ◽  
Autosomal Dominant Disorder ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Copa Syndrome

COPA syndrome is a rare autosomal dominant disorder with auto-immune and auto-inflammatory abnormalities. This disease is caused by mutations of COPα, a protein that functions in the retrograde transport from the Golgi to the ER. Here we report the first COPA case of an 11-year-old boy with c.841C>T, p.R281W mutation. The arginine at position 281 was located in a highly evolutionary-conserved region. Immunosuppressive drugs and corticosteroids might not improve the long-term outcome of COPA patients. For patients with pulmonary disease, polyarthritis and/or kidney disorder, and suspected of COPA, genetic analysis should be conducted promptly for early diagnosis.

Abstract 9958: Fitness in Young Adulthood is Independently Associated With Improved Survival and Cardiovascular Risk: The CARDIA study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ravi Shah ◽  
Venkatesh Murthy ◽  
Laura Colangelo ◽  
Jared Reis ◽  
Bharath Venkatesh-Ambale ◽  
...  
Keyword(s):  
Young Adulthood ◽  
Cardiovascular Health ◽  
Critical Role ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Test Duration ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Lower Hazard

Introduction: Though cardiorespiratory fitness (CRF) is a well-established prognostic marker in older adults, the relationship between changes in CRF during early adulthood and long-term cardiovascular structure, function, and events remain unknown. Hypothesis: CRF and its change over time in young adults is associated with long-term outcome and cardiovascular disease (CVD). Methods: 4,872 American adults age 18-30 years underwent treadmill exercise testing at a baseline study visit in 1985-1986, and 2,472 individuals who underwent repeat treadmill testing 7 years later in CARDIA. Participants were followed for a median of 26.9 years, with assessment of obesity, echocardiographic left ventricular (LV) mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Incident CVD (cardiovascular death, heart failure, myocardial infarction, peripheral artery disease and stroke) and all-cause mortality were uniformly adjudicated. Results: From 4,872 individuals, 273 (5.6%) died and 193 (4%) experienced CVD events at a median 26.9 year follow-up. After full adjustment, each additional minute of baseline exercise test duration was associated with a 13% lower hazard of death (hazard ratio HR 0.87, 95% CI 0.81-0.92, P<0.0001) and a 9% lower hazard of CVD (HR 0.91, 95% CI 0.84-0.98, P=0.008). Higher baseline fitness was associated with decreased risk of LV hypertrophy (P=0.009) and higher global longitudinal strain (P<0.0001) at Year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by Year 7 was associated with a 20% increased hazard of death and CVD, along with a greater probability of LV hypertrophy and more impaired strain. There was no association between change in fitness and CAC. Conclusions: Higher fitness at baseline and improvement in fitness early in adulthood are favorably associated with CVD and mortality risk. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction, but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.

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