Since activation of the peroxisome proliferator-activated receptor γ (PPARγ) results in supression of inflammatory moleculs in glial cells, neurons and macrophages, we tested, if PPARγ-activating substances have a protective effect in the EAE-mouse model for multiple sclerosis. We were able to demonstrate, that oral treatment of mice resulted in ameloriated clinical symptoms of EAE and reduced the periventricular and periventricular infiltration of lympho- and leucocytes into the central nervous system (1).
Studies on human T-lymphocytes of healthy controls and multiple sclerosis patients showed, that treatment with PPARγ-agonists reduced the inflammation-induced proliferation of these cells and induced BAX and BCL-2 mediated apoptosis (2). Further on, PPARγ-agonists were able to reduce the secretion of pro-inflammatory cytokines.
Taken together, these results indicate a therapeutic option for PPARγ-agonists for the treatment of multiple sclerosis, as they are already used for the treatment of Type 2 diabetes.
  1. D.L. Feinstein, E. Galea, V. Gavriluyk, C.F. Brosnan, C.C. Whitacre; L. Dumitrescu-Ozimek, G.E. Landreth, G. Weinberg and M.T. Heneka (2002) PPARβ agonists prevent experimental autoimmune encephalitis. Ann. Neurol. 51: 694-702.
  2. S. Schmidt, E. Moric, G.E. Landreth, M.Schmidt, M. Sastre, D.L. Feinstein, T. Klockgether and M.T. Heneka (2002) PPARγ agonists inhibit T-cell proliferation and proinflammatory cytokine secretion of lymphocytes derived from MS patients and healty subjects. (J Leukoc Biol. 2004 Mar;75(3):478-85).
  3. PPARγ and RXRγ ligands act synergistically as potent antineoplastic agents in vitro and in vivo glioma models. Papi A, Tatenhorst L, Terwel D, Hermes M, Kummer MP, Orlandi M, Heneka MT. J. Neurochem. 2009, May 11. PMID: 19457135

Funding