Neurobiology of Disease (Jul 2006)

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

  • Marianne Husson,
  • Valérie Enderlin,
  • André Delacourte,
  • Nadirah Ghenimi,
  • Serge Alfos,
  • Véronique Pallet,
  • Paul Higueret

Journal volume & issue
Vol. 23, no. 1
pp. 1 – 10

Abstract

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Recent data have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to a deposition of β-amyloid (Aβ). The aim of this study was to precise the role of vitamin A and its nuclear receptors (RAR) in the processes leading to the Aβ 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 RARβ, and of proteins involved in amyloidogenic pathway, e.g., amyloid precursor protein (APP), β-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 RARβ, 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.

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