Retinoid X receptor ligand regulates RXRα/Nur77-dependent apoptosis via modulating its nuclear export and mitochondrial targeting

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder disease in elderly. It is characterized by the formation of amyloid plaques and nerve cells apoptosis in the brain. This study focuses on the association between nerve cells apoptosis and nuclear receptors within AD. Thus, we detected the changes of the expression and subcellular localization of RXRα/Nur77 and the apoptotic rate of neuroblastoma cells, SH-SY5Y cells and nerve cells in C57BL/6 mouse hippocampus in Alzheimer’s disease pathologic condition, and investigated the effect of RXRα exporting inhibition caused by 9-cis-RA on the apoptosis of neurons. We demonstrated that Aβ peptide and H2O2 treatment could result in the translocation of RXRα and Nur77 from the nucleus to the mitochondria, and the ligand of RXR, 9-cis-RA, treatment can block the above phenomenon. More importantly, 9-cis-RA treatment could reduce the apoptotic rate of neurons caused by H2O2 or Aβ stimulation via enhancing the expression level of Bcl-2 protein. Therefore, our studies revealed a critical role of RXRα/Nur77 in 9-cis-RA-mediated anti-apoptosis in nerve cells and provided novel information for better management of AD.