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. 2022 Aug 15;11(16):2530. doi: 10.3390/cells11162530

Figure 8.

Figure 8

Overview of RA signaling pathway and RAR/RXR agonists and RAMBAs. In the bloodstream, retinol forms complex with RBP4 and enters the cells via STRA6 or by membrane diffusion. Within cells, retinol is converted to retinaldehyde by ADHs and RDHs and subsequently oxidized to RA by ALDH1A1-3. Three naturally occurring RA stereoisomers are ATRA, 13-cis RA and 9-cis RA. RA enters the nucleus via CRABP2, where it interacts with RAR/RXR heterodimer forming a complex that binds to RARE in the promoter regions of RA target genes. RA is inactivated by CYP26 oxidase (modified based on [380]). Summary of inhibitors of the CYP26A1 enzyme (RAMBAs) and RARs/RXRs agonists is made based on [383] and https://resources.tocris.com/pdfs/literature/reviews/retinoid-receptors-review-2019-web.pdf (accessed on 23 May 2022), respectively. RAR and RXR agonists and RAMBAs used for treatment of GBM cells in vitro or in vivo are presented in green letters, and RAR and RXR agonists and RAMBAs used in clinical trials for GBMs are presented in blue letters, while RAR and RXR agonists and RAMBAs not yet used in treatment of GBM are presented in black letters (based on results of previously reported publications included in the main text and results obtained by [385,386,387,388,389,390]).