THE THERAPEUTIC TREATMENT OF PEPITEM INCREASES THE PROTEIN EXPRESSION OF SIRT1 IN A MOUSE MODEL OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE) AS A MODEL FOR HUMAN MS
DOI:
https://doi.org/10.20319/icrlsh.2024.1625Keywords:
PEPITEM, Experimental Autoimmune Encephalomyelitis,, SIRT1, Anti-InflammatoryAbstract
Objective: To investigate the effect of the prophylactic and therapeutic treatment of the immunopeptide PEPITEM on the protein expression of SIRT1 in a mouse model of experimental autoimmune encephalomyelitis (EAE) as a model for human MS.
Methods: Using C57BL/6 female mice, we dosed the PEPITEM in the EAE model via intraperitoneal injections either prophylactically or therapeutically. The disease was induced using MOG35-55 and complete Freund's adjuvants augmented with pertussis toxin. The EAE score was recorded daily until the end of the experiment (21 days). A Western blot analysis was performed on the brain lysate to measure the protein concentration of SIRT1.
Results: The therapeutic treatment with PEPITEM increased the protein expressions of SIRT1 on the EAE mice whereas the prophylactic injections did not affect the protein expression of SIRT1.
Conclusion: Collectively, the therapeutic treatment with PEPITEM suggesting anti-inflammatory effect of PEPITEM on the brain damage in EAE mice which offers a novel and safe strategy for drug therapy in MS, opening new avenues for research and treatment.
References
Abe-Higuchi, N., et al., Hippocampal Sirtuin 1 Signaling Mediates Depression-like Behavior. Biological Psychiatry, 2016. 80(11): p. 815-826.
Bradbury, C.A., et al., Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia, 2005. 19(10): p. 1751-1759.
Cheng, Y., et al., Sirtuin 1 attenuates oxidative stress via upregulation of superoxide dismutase 2 and catalase in astrocytes. Journal of Neuroimmunology, 2014. 269(1): p. 38-43.
Chimen, M., et al., Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease. Nat Med, 2015. 21(5): p. 467-475.
Cho, S.-H., et al., SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β. The Journal of Neuroscience, 2015. 35(2): p. 807-818.
Croft, A.P., et al., 246. PROPHYLACTIC TREATMENT WITH PEPITEM INHIBITS ONSET OF COLLAGEN-INDUCED ARTHRITIS AND THERAPEUTICALLY PEPITEM REDUCES DISEASE SEVERITY. Rheumatology, 2017. 56(suppl_2).
Deng, C.X., SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci, 2009. 5(2): p. 147-52.
Huffman, D.M., et al., SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res, 2007. 67(14): p. 6612-8.
Leray, E., et al., Epidemiology of multiple sclerosis. Rev Neurol (Paris), 2016. 172(1): p. 3-13.
Lu, G., et al., Role and Possible Mechanisms of Sirt1 in Depression. Oxidative Medicine and Cellular Longevity, 2018. 2018: p. 8596903.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright of Published Articles
Author(s) retain the article copyright and publishing rights without any restrictions.
All published work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.