Bianchi, Beatrice; Smith, Paul A; Abriel, Hugues (2018). The ion channel TRPM4 in murine experimental autoimmune encephalomyelitis and in a model of glutamate-induced neuronal degeneration. Molecular brain, 11(1), p. 41. BioMed Central 10.1186/s13041-018-0385-4
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Transient receptor potential melastatin member 4 (TRPM4), a Ca-activated nonselective cation channel, has been found to mediate cell membrane depolarization in immune response, insulin secretion, cardiovascular diseases, and cancer. In murine experimental autoimmune encephalomyelitis (EAE), TRPM4 deletion and administration of glibenclamide were found to ameliorate clinical symptoms and attenuate disease progression. However, the exact role of TRPM4 in EAE, as well as the molecular mechanisms underlining TRPM4 contribution in EAE, remain largely unclear. In the present study, EAE was induced in WT C57BL/6 N mice using myelin oligodendrocyte glycoprotein 35-55 (MOG) and TRPM4 protein and mRNA expression were examined in spinal cord membrane extracts. Our results showed that TRPM4 protein and mRNA are upregulated in EAE, and that their upregulation correlated with disease progression. Moreover, newly-developed TRPM4 inhibitors, named compound 5 and compound 6, were shown to exert a better neuroprotection compared to currently used TRPM4 inhibitors in an in vitro model of glutamate-induced neurodegeneration. These results support the hypothesis that TRPM4 is crucial from early stages of EAE, and suggest that these more potent TRPM4 inhibitors could be used as novel protective therapeutic tools in glutamate-induced neurodegeneration.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Faculty Institutions > NCCR TransCure 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Bianchi, Beatrice, Abriel, Hugues |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1756-6606 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Verena de Serra Frazao-Bill |
Date Deposited: |
14 Feb 2019 09:37 |
Last Modified: |
05 Dec 2022 15:24 |
Publisher DOI: |
10.1186/s13041-018-0385-4 |
PubMed ID: |
29996905 |
Uncontrolled Keywords: |
Experimental autoimmune encephalomyelitis Glutamate-induced neurodegeneration HT22 Inhibitors Multiple sclerosis TRPM4 |
BORIS DOI: |
10.7892/boris.123542 |
URI: |
https://boris.unibe.ch/id/eprint/123542 |
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