All-trans Retinoic acid (atRA), the active metabolite of vitamin A, activates the Retinoic Acid Receptors (RARs). These receptors are ligand-activated transcription factors that regulate the transcription of target genes responsible for modulation of cell proliferation and differentiation. Several lines of evidence point to the therapeutic potential of atRA in the treatment of neurological disease. Skin keratinization disorders are efficiently treated by atRA derivatives. In the CNS, atRA synthesis is induced by loss of synaptic activity and a decrease in dendritic calcium levels, supporting its role as a modulator of neuronal function. The involvement of impaired atRA signaling in brain health is further supported by deficits in learning and memory observed in RAR null or Vitamin A-deficient mice. However, the therapeutic chronic uses of atRA and its synthetic derivatives are limited due to potential side effects such as irritation or bone spurs. When atRA is administered to humans it increases the expression of the cytochrome P450 responsible of atRA metabolism, CYP26, which may lead to resistance to atRA treatment. In order to increase atRA concentration without inducing atRA-mediated side effects, we have identified inhibitors of CYP26. In this seminar, we will report details of the design, in vitro characterization, and in vivo testing of this new series of compounds and demonstrate their efficacy to treat traumatic brain injury and skin keratinization disorders.

Inhibition of CYP26 to treat both proliferative skin disease and traumatic brain injury

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.