Literature summary extracted from
Imam, S.; Prathibha, R.; Dar, P.; Almotah, K.; Al-Khudhair, A.; Hasan, S.A.; Salim, N.; Jilani, T.N.; Mirmira, R.G.; Jaume, J.C.
eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of type 1 diabetes (2019), Sci. Rep., 9, 1533 .
Application
EC Number |
Application |
Comment |
Organism |
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2.5.1.46 |
medicine |
in a transgenic mouse model of type 1 diabetes, in which human GAD65 is expressed in pancreatic beta-cells, and human MHC-II is expressed on antigen presenting cells, deoxyhypusine synthase inhibitor N''-guanyl-1,7-diaminoheptane, i.e. GC7, alters the pathophysiology by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. Inhibition of eIF5A resets the proinflammatory bias in the pancreatic microenvironment. There is reduction of Th1/Th17 response, an increase in Treg numbers, debase in IL17 and IL21 cytokines levels in serum, lowering of anti-GAD65 antibodies, and ablation of the ER stress that improves functionality of the beta-cells, but minimal effect on the cytotoxic CD8 T-cell mediated response |
Mus musculus |
Inhibitors
EC Number |
Inhibitors |
Comment |
Organism |
Structure |
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2.5.1.46 |
N''-guanyl-1,7-diaminoheptane |
i.e. GC7. Downregulation of eIF5A through inhibition of deoxyhypusine synthase favors the reversal of the Th1 mediated cellular processes but minimally affects CD8 T-cells. Inhibition of elF5A increases the Treg/Th17 ratio, reduces anti-GAD65 antibody production and islet/beta-cell ER stress that leads to improvement in the endocrine pancreas functionality in a humanized model of T1D. Diabetes onset is delayed |
Mus musculus |
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Organism
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Organism |
UniProt |
Comment |
Textmining |
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2.5.1.46 |
Mus musculus |
Q3TXU5 |
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- |
Source Tissue
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Source Tissue |
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Organism |
Textmining |
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