| First Author | Goncalves MB | Year | 2013 |
| Journal | Eur J Neurosci | Volume | 37 |
| Issue | 7 | Pages | 1182-92 |
| PubMed ID | 23379615 | Mgi Jnum | J:214921 |
| Mgi Id | MGI:5604209 | Doi | 10.1111/ejn.12142 |
| Citation | Goncalves MB, et al. (2013) Amyloid beta inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor alpha agonist. Eur J Neurosci 37(7):1182-92 |
| abstractText | The retinoic acid receptor (RAR) alpha system plays a key role in the adult brain, participating in the homeostatic control of synaptic plasticity, essential for memory function. Here we show that RARalpha signalling is down-regulated by amyloid beta (Abeta), which inhibits the synthesis of the endogenous ligand, retinoic acid (RA). This results in the counteraction of a variety of RARalpha-activated pathways that are key in the aetiopathology of Alzheimer's disease (AD) but which can be reversed by an RARalpha agonist. RARalpha signalling improves cognition in the Tg2576 mice, it has an anti-inflammatory effect and promotes Abeta clearance by increasing insulin degrading enzyme and neprilysin activity in both microglia and neurons. In addition, RARalpha signalling prevents tau phosphorylation. Therefore, stimulation of the RARalpha signalling pathway using a synthetic agonist, by both clearing Abeta and counteracting some of its toxic effects, offers therapeutic potential for the treatment of AD. |
