C.I.J. and M.B.G. contributed equally to this work.
Retinoic acid receptor-α signalling antagonizes both intracellular and extracellular amyloid-β production and prevents neuronal cell death caused by amyloid-β
Article first published online: 15 OCT 2010
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 32, Issue 8, pages 1246–1255, October 2010
How to Cite
Jarvis, C. I., Goncalves, M. B., Clarke, E., Dogruel, M., Kalindjian, S. B., Thomas, S. A., Maden, M. and Corcoran, J. P. T. (2010), Retinoic acid receptor-α signalling antagonizes both intracellular and extracellular amyloid-β production and prevents neuronal cell death caused by amyloid-β. European Journal of Neuroscience, 32: 1246–1255. doi: 10.1111/j.1460-9568.2010.07426.x
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- Issue published online: 15 OCT 2010
- Article first published online: 15 OCT 2010
- Received 16 March 2010, revised 28 June 2010, 27 July 2010, accepted 3 August 2010
- Alzheimer's disease;
- neuronal survival;
- retinoic acid;
- small molecule
Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) deposition in the brain, neuronal cell loss and cognitive decline. We show here that retinoic acid receptor (RAR)α signalling in vitro can prevent both intracellular and extracellular Aβ accumulation. RARα signalling increases the expression of a disintegrin and metalloprotease 10, an α-secretase that processes the amyloid precursor protein into the non-amyloidic pathway, thus reducing Aβ production. We also show that RARα agonists are neuroprotective, as they prevent Aβ-induced neuronal cell death in cortical cultures. If RARα agonists are given to the Tg2576 mouse, the normal Aβ production in their brains is suppressed. In contrast, neither RARβ nor γ-agonists affect Aβ production or Aβ-mediated neuronal cell death. Therefore, RARα agonists have therapeutic potential for the treatment of AD.