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Amelioration of experimental autoimmune encephalomyelitis by gemfibrozil in mice via PPARβ/δ: implications for multiple sclerosis.
- Source :
- Frontiers in Cellular Neuroscience; 2024, p01-15, 15p
- Publication Year :
- 2024
-
Abstract
- It is important to describe effective and non-toxic therapies for multiple sclerosis (MS), an autoimmune demyelinating disease. Experimental autoimmune encephalomyelitis (EAE) is an immune-mediated inflammatory disease that serves as a model for MS. Earlier we and others have shown that, gemfibrozil, a lipid-lowering drug, exhibits therapeutic efficacy in EAE. However, the underlying mechanism was poorly understood. Although gemfibrozil is a known ligand of peroxisome proliferator-activated receptor a (PPARa), here, we established that oral administration of gemfibrozil preserved the integrity of blood--brain barrier (BBB) and blood--spinal cord barrier (BSB), decreased the infiltration of mononuclear cells into the CNS and inhibited the disease process of EAE in both wild type and PPARα<superscript>-/-</superscript> mice. On the other hand, oral gemfibrozil was found ineffective in maintaining the integrity of BBB/BSB, suppressing inflammatory infiltration and reducing the disease process of EAE in mice lacking PPARb (formerly PPARd), indicating an important role of PPARβ/δ, but not PPARα, in gemfibrozil-mediated preservation of BBB/BSB and protection of EAE. Regulatory T cells (Tregs) play a critical role in the disease process of EAE/MS and we also demonstrated that oral gemfibrozil protected Tregs in WT and PPARα<superscript>-/-</superscript> EAE mice, but not PPARβ<superscript>-/-</superscript> EAE mice. Taken together, our findings suggest that gemfibrozil, a known ligand of PPARα, preserves the integrity of BBB/BSB, enriches Tregs, and inhibits the disease process of EAE via PPARβ, but not PPARα. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16625102
- Database :
- Complementary Index
- Journal :
- Frontiers in Cellular Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 177661692
- Full Text :
- https://doi.org/10.3389/fncel.2024.1375531