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Retinoic acid receptor‐α signalling antagonizes both intracellular and extracellular amyloid‐β production and prevents neuronal cell death caused by amyloid‐β
Author(s) -
Jarvis C. I.,
Goncalves M. B.,
Clarke E.,
Dogruel M.,
Kalindjian S. B.,
Thomas S. A.,
Maden M.,
Corcoran J. P. T.
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07426.x
Subject(s) - neuroprotection , microbiology and biotechnology , extracellular , programmed cell death , intracellular , retinoic acid , adam10 , amyloid precursor protein , chemistry , cognitive decline , amyloid (mycology) , alzheimer's disease , biology , neuroscience , disintegrin , metalloproteinase , biochemistry , medicine , dementia , apoptosis , matrix metalloproteinase , disease , gene , inorganic chemistry
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.