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 language | English |
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Pages (from-to) | 1246 - 1255 |
Number of pages | 10 |
Journal | European Journal of Neuroscience |
Volume | 32 |
Issue number | 8 |
DOIs | |
Publication status | Published - Oct 2010 |