scholarly journals Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3217
Author(s):  
Simela Chatzikonstantinou ◽  
Vasiliki Poulidou ◽  
Marianthi Arnaoutoglou ◽  
Dimitrios Kazis ◽  
Ioannis Heliopoulos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Immune Responses ◽  
Intestinal Barrier ◽  
Therapeutic Effects ◽  
Neural Cells ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1–5 (S1PR1–5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymphocytes from secondary lymphoid organs. Since the inflammatory process is a key element of immune-mediated diseases, including multiple sclerosis (MS), S1PR modulators are currently used to ameliorate systemic immune responses. The ubiquitous expression of S1PRs by immune, intestinal and neural cells has significant implications for the regulation of the gut–brain axis. The dysfunction of this bidirectional communication system may be a significant factor contributing to MS pathogenesis, since an impaired intestinal barrier could lead to interaction between immune cells and microbiota with a potential to initiate abnormal local and systemic immune responses towards the central nervous system (CNS). It appears that the secondary mechanisms of S1PR modulators affecting the gut immune system, the intestinal barrier and directly the CNS, are coordinated to promote therapeutic effects. The scope of this review is to focus on S1P−S1PR functions in the cells of the CNS, the gut and the immune system with particular emphasis on the immunologic effects of S1PR modulation and its implication in MS.

FTY720 on the way from the base camp to the summit of the mountain: relevance for remyelination

2012 ◽  
Vol 18 (3) ◽  
pp. 258-263 ◽  
Author(s):  
M Kipp ◽  
S Amor
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Oral Disease ◽  
S1p Receptors ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

FTY720 (fingolimod; Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral disease-modifying therapy to be approved for the treatment of relapsing–remitting multiple sclerosis. FTY720 is rapidly converted in vivo to the active S-fingolimod-phosphate, which binds to S1P receptors. This action inhibits egress of lymphocytes from the lymph nodes, preventing entry into the blood and thus infiltration into the central nervous system. More recent studies, however, convincingly show that FTY720 crosses the blood–brain barrier, where it is thought to act on S1P receptors on cells within the central nervous system, such as astrocytes, oligodendrocytes or microglia. Here we discuss the evidence showing that FTY720 also plays a role in remyelination and repair within the brain. While the mechanisms of action still require firm elucidation, it is clear that FTY720 could also be reparative, extending its therapeutic potential for multiple sclerosis.

scholarly journals Does Siponimod Exert Direct Effects in the Central Nervous System?

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1771 ◽  
Author(s):  
Markus Kipp
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Direct Interaction ◽  
Active Role ◽  
Progressive Multiple Sclerosis ◽  
Receptor Subtypes ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

The modulation of the sphingosine 1-phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti-inflammatory effect of retaining lymphocytes in lymph nodes. Different sphingosine 1-phosphate receptor subtypes are expressed in the brain and spinal cord, and their pharmacological effects may improve disease development and neuropathology. Siponimod (BAF312) is a novel sphingosine 1-phosphate receptor modulator that has recently been approved for the treatment of active secondary progressive multiple sclerosis (MS). In this review article, we summarize recent evidence suggesting that the active role of siponimod in patients with progressive MS may be due to direct interaction with central nervous system cells. Additionally, we tried to summarize our current understanding of the function of siponimod and discuss the effects observed in the case of MS.

Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy

2013 ◽  
Vol 19 (9) ◽  
pp. 1230-1233 ◽  
Author(s):  
Akiko Yokoseki ◽  
Etsuji Saji ◽  
Musashi Arakawa ◽  
Mariko Hokari ◽  
Takanobu Ishiguro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Ccr7 Expression ◽  
Blood Lymphocytes ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
Secondary Lymphoid Organs

Fingolimod acts as a functional antagonist of the sphingosine-1-phosphate receptor, and it traps lymphocytes in secondary lymphoid organs and precludes their migration into the central nervous system. We report the case of a patient who suffered a relatively severe relapse of multiple sclerosis (MS) during the initial 3 months of fingolimod therapy, with retention of CCR7 expression on CD4+ T cells in the cerebrospinal fluid (CSF) despite decreased numbers of lymphocytes and decreased expression of CCR7 on CD4+ T cells in the blood. These data suggest that fingolimod may cause differential effects on the CSF and blood lymphocytes of patients with MS during the initial months of therapy.

First Presentation of an Acquired Demyelinating Syndrome

2017 ◽  
Vol 16 (03) ◽  
pp. 164-170
Author(s):  
Rachel Gottlieb-Smith ◽  
Amy Waldman
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Differential Diagnosis ◽  
Optic Neuritis ◽  
Clinical Features ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
Acute Disseminated Encephalomyelitis ◽  
The Central Nervous System

AbstractAcquired demyelinating syndromes (ADS) present with acute or subacute monofocal or polyfocal neurologic deficits localizing to the central nervous system. The clinical features of distinct ADS have been carefully characterized including optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. These disorders may all be monophasic disorders. Alternatively, optic neuritis, partial transverse myelitis, and acute disseminated encephalomyelitis may be first presentations of a relapsing or polyphasic neuroinflammatory disorder, such as multiple sclerosis or neuromyelitis optica. The clinical features of these disorders and the differential diagnosis are discussed in this article.

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