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The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway is an important pathway involved in antioxidant and anti-inflammatory responses. Modulation of the Nrf2/ARE pathway is an attractive therapeutic target for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) [2][3].
CDDO-TFEA is an Nrf2/ARE pathway activator. In NSC-34 G93A SOD1 cells, CDDO-TFEA upregulated Nrf2 expression and caused translocation of Nrf2 into the nucleus. CDDO-TFEA also increased the expression of Nrf2/ARE-regulated proteins (NQO-1, HO-1 and Glutathione reductase).
In mice with experimental autoimmune encephalomyelitis (EAE), CDDO-TFEA reduced immune and inflammatory cell populations. CDDO-TFEA also significantly reduced Th1 and Th17 cytokines (IL6, IL17, IFNγ, TNFα and GMCSF) [1]. In ALS mice model, CDDO-TFEA upregulated the expression and resulted in translocation of Nrf2 to the nucleus of neurons in the spinal cord. In G93A SOD1 mice, CDDO-TFEA increased the life-span by 17.6 days [2].
References:
[1]. Pareek TK, Belkadi A, Kesavapany S, et al. Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis. Sci Rep. 2011;1:201.
[2]. Neymotin A, Calingasan NY, Wille E, et al. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med. 2011 Jul 1;51(1):88-96.
[3]. Stack C, Ho D, Wille E, et al. Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington's disease. Free Radic Biol Med. 2010 Jul 15;49(2):147-58.
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