Retinoic acid receptor-alpha signalling antagonizes both intracellular and extracellular amyloid-beta production and prevents neuronal cell death caused by amyloid-beta

C. I. Jarvis, M. B. Goncalves, E. Clarke, M. Dogruel, S. B. Kalindjian, S. A. Thomas, M. Maden, J. P. T. Corcoran

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68 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by amyloid-beta (A beta) deposition in the brain, neuronal cell loss and cognitive decline. We show here that retinoic acid receptor (RAR)alpha signalling in vitro can prevent both intracellular and extracellular A beta accumulation. RAR alpha signalling increases the expression of a disintegrin and metalloprotease 10, an alpha-secretase that processes the amyloid precursor protein into the non-amyloidic pathway, thus reducing A beta production. We also show that RAR alpha agonists are neuroprotective, as they prevent A beta-induced neuronal cell death in cortical cultures. If RAR alpha agonists are given to the Tg2576 mouse, the normal A beta production in their brains is suppressed. In contrast, neither RAR beta nor gamma-agonists affect A beta production or A beta-mediated neuronal cell death. Therefore, RAR alpha agonists have therapeutic potential for the treatment of AD.
Original languageEnglish
Pages (from-to)1246 - 1255
Number of pages10
JournalEuropean Journal of Neuroscience
Volume32
Issue number8
DOIs
Publication statusPublished - Oct 2010

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