The Nrf2 pathway as a potential therapeutic target for Huntington disease A commentary on 'Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington disease'.

摘要

Stack and collaborators, in their article in this issue of Free Radical Biology & Medicine, show that two synthetic triterpenoids, 2-cyano-3,12-dioxooleana-l,9-dien-28-oic acid (CDDO) ethyl amide (CDDO-EA) and CDDO trifluoroethylamide (CDDO-TFEA), molecules that probably activate the antioxidant master regulator Nrf2, are neuro-protective in a transgenic mouse model of Huntington disease (HD) [1]. These exciting results provide a new therapeutic hope for HD, a fatal neurological disorder that desperately needs original and efficient treatments that could slow down disease progression. The data in this article not only provide hope for the development of therapeutics for HD but also stimulate future research as a number of unanswered questions remain. In particular, an intriguing question is the cellular mechanisms underlying the therapeutic effects in mice. One interesting hypothesis that would deserve further study is that these molecules may primarily act on nonneuronal cells, by enhancing antioxidant properties in astrocytes and reducing deleterious micro-glia activation.