A class of signaling molecules, whose relevance for neurodegenerative diseases has recently become apparent, is the transcriptional regulators of the nuclear receptor superfamily. This group includes retinoic acid receptors (RAR) and peroxisome proliferator-activated receptors (PPAR), both of which form heterodimers with retinoid X receptors (RXR). The RAR/RXR transcription factor complex is activated by ligand binding, its natural ligand being all-trans retinoic acid (all-trans RA). Retinoids are obtained from the diet in form of vitamin A (retinol and retinal), retinyl esters or b-carotene. Retinoid receptors belong to the same superfamily as PPAR, vitamin D receptor, thyroid hormone receptor (TR) and steroid receptors. 
They can be grouped into two families, the RAR and the RXR, each consisting of three isoforms encoded by separate genes: RARa, RARb, RARg (also: NR1B1–3) and RXRa, RXRb, RXRg (NR2B1–3). About 500 genes have been suggested to be regulated by RAR/RXR signaling,  including enzymes, transcription factors, cytokines and cytokine receptors. A direct influence on phosphorylation of the transcription factor CREB and the mitogenactivated kinase ERK1/2 has been observed. Another path of action is the repression of AP-1 (Jun, Fos) activity, which involves RAR/RXR heterodimers, but not the RARE. In an oxygen/glucose deprivation/reperfusion model to simulate ischemia, RA protected hippocampal neurons from cell death and RA also increased phosphorylation of ERK1/2 but reduced phosphorylation of the kinases JNK and p38.


1.van Neerven S,et al. Prog Neurobiol. 2008;85(4):433–451.