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FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment
- Source :
- Current Medicinal Chemistry
- Publication Year :
- 2020
- Publisher :
- Bentham Science Publishers, 2020.
-
Abstract
- FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. FTY720 is mainly associated with unique functional “antagonist” and “agonist” mechanisms. The functional antagonistic mechanism is mediated by the transient down-regulation and degradation of S1P receptors on lymphocytes, which prevents lymphocytes from entering the blood stream from the lymph node. This subsequently results in the development of lymphopenia and reduces lymphocytic inflammation. Functional agonistic mechanisms are executed through S1P receptors expressed on the surface of various cells including neurons, astrocytes, microglia, and blood vessel endothelial cells. These functions might play important roles in regulating anti-apoptotic systems, modulating brain immune and phagocytic activities, preserving the Blood-Brain-Barrier (BBB), and the proliferation of neural precursor cells. Recently, FTY720 have shown receptor-independent effects, including intracellular target bindings and epigenetic modulations. Many researchers have recognized the positive effects of FTY720 and launched basic and clinical experiments to test the use of this agent against stroke. Although the mechanism of FTY720 has not been fully elucidated, its efficacy against cerebral stroke is becoming clear, not only in animal models, but also in ischemic stroke patients through clinical trials. In this article, we review the data obtained from laboratory findings and preliminary clinical trials using FTY720 for stroke treatment.
- Subjects :
- Agonist
FTY720
medicine.drug_class
Inflammation
Biochemistry
Article
03 medical and health sciences
0302 clinical medicine
Immune system
Neural Stem Cells
hemic and lymphatic diseases
Drug Discovery
medicine
Animals
Humans
fingolimod
Receptor
sphingosinc-l-phosphatc
Stroke
030304 developmental biology
Pharmacology
0303 health sciences
Microglia
business.industry
Fingolimod Hydrochloride
Multiple sclerosis
Organic Chemistry
Endothelial Cells
medicine.disease
Fingolimod
stroke
Receptors, Lysosphingolipid
medicine.anatomical_structure
inflammation
sphingosine kinase
Propylene Glycols
Brain Injuries
sphingosine-1-phosphate
sphingosinc kinase
Molecular Medicine
medicine.symptom
business
Neuroscience
030217 neurology & neurosurgery
Immunosuppressive Agents
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 1875533X and 09298673
- Volume :
- 27
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Current Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....5fad73464596fcf9fbc7f81f7f6158e7