Retinoic acid normalizes nuclear receptor mediated hypo-expression of proteins involved in beta-amyloid deposits in the cerebral cortex of vitamin A deprived rats

Neurobiol Dis. 2006 Jul;23(1):1-10. doi: 10.1016/j.nbd.2006.01.008. Epub 2006 Mar 10.


Recent data have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to a deposition of beta-amyloid (Abeta). The aim of this study was to precise the role of vitamin A and its nuclear receptors (RAR) in the processes leading to the Abeta deposits. Thus, the effect of vitamin A depletion and subsequent administration of retinoic acid (RA, the active metabolite of vitamin A) on the expression of RARbeta, and of proteins involved in amyloidogenic pathway, e.g., amyloid precursor protein (APP), beta-secretase enzyme (BACE), and APP carboxy-terminal fragment (APP-CTF) was examined in the whole brain, hippocampus, striatum, and cerebral cortex of rats. Rats fed a vitamin A-deprived diet for 13 weeks exhibited decreased amount of RARbeta, APP695, BACE, and of APP-CTF in the whole brain and in the cerebral cortex. Administration of RA is able to restore all expression. The results suggest that fine regulation of vitamin A mediated gene expression seems fundamental for the regulation of APP processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / drug effects*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases
  • Blotting, Western
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Endopeptidases / drug effects
  • Endopeptidases / metabolism
  • Male
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptors, Retinoic Acid / drug effects*
  • Receptors, Retinoic Acid / metabolism
  • Tretinoin / pharmacology*
  • Vitamin A / metabolism
  • Vitamin A Deficiency / physiopathology*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Vitamin A
  • Tretinoin
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, rat