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The \u03b1\u2010secretase ADAM10 has been found to be regulated by retinoic acid, the bioreactive metabolite of vitamin A. Here we show that retinoids induce gene expression of ADAM10 and \u03b1\u2010secretase activity by nonpermissive retinoid acid receptor\/retinoid X receptor (RAR\/RXR) heterodimers, whereby \u03b1\u2010and \u03b2\u2010isotypes of RAR play a major role. However, ligands of other RXR binding partners, such as the vitamin D receptor, do not stimulate \u03b2\u2010secretase activity. On the basis of these findings, we examined the effect of synthetic retinoids and found a strong enhancement of nonamyloidogenic processing of the amyloid precursor protein by the vitamin A analog acitretin: it stimulated ADAM10 promoter activity with an EC\n                    <jats:sub>50<\/jats:sub>\n                    of 1.5 \u03bc.M and led to an increase of mature ADAM10 protein that resulted in a two\u2010to three\u2010fold increase of the ratio between \u03b1\u2010and \u03b2\u2010secretase activity in neuroblastoma cells. The \u03b1\u2010secretase stimulation by acitretin was completely inhibited by the ADAM10\u2010specific inhibitor GI254023X. Intracerebral injection of acitretin in APP\/PS1\u201021 transgenic mice led to a reduction of A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    . The results of this study may have clinical relevance because acitretin has been approved for the treatment of psoriasis since 1997 and found generally safe for long\u2010term use in humans.\u2014Tippmann, F.,Hundt, J., Schneider, A., Endres, K., Fahrenholz, F. Up\u2010regulation of the \u03b1\u2010secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 23, 1643\u20131654 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-121392","type":"journal-article","created":{"date-parts":[[2009,1,14]],"date-time":"2009-01-14T22:35:17Z","timestamp":1231972517000},"page":"1643-1654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":211,"title":["Up\u2010regulation of the \u03b1\u2010secretase ADAM10 by retinoic acid receptors and acitretin"],"prefix":"10.1096","volume":"23","author":[{"given":"Frank","family":"Tippmann","sequence":"first","affiliation":[{"name":"Institute of Biochemistry Johannes Gutenberg\u2010University Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Hundt","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Johannes Gutenberg\u2010University Mainz 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