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It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein\u2010coupled melatonin receptors (MTRs), MT\n                    <jats:sub>1<\/jats:sub>\n                    and MT\n                    <jats:sub>2<\/jats:sub>\n                    , but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid\n                    <jats:italic>\u03b2<\/jats:italic>\n                    peptides (A\u03b2\n                    <jats:sub>1\u201040<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    ). A\u03b2 treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up\u2010regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle\u2010treated glands. Blocking NF\u2010\u03baB activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT\n                    <jats:sub>1<\/jats:sub>\n                    or MT\n                    <jats:sub>2<\/jats:sub>\n                    receptors to A\u03b2 lead to a 40% reduction in [\n                    <jats:sup>125<\/jats:sup>\n                    I]iodomelatonin binding to MT\n                    <jats:sub>1<\/jats:sub>\n                    . ERK1\/2 activation triggered by MTRs, but not by the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u2010adrenergic receptor, was markedly impaired by A\u03b2 in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of A\u03b2, opening new perspectives to Alzheimer disease diagnosis and therapeutic intervention.\u2014Cecon, E., Chen, M., Mar\u00e7ola, M., Fernandes, P. A. C., Jockers, R., Markus, R. P. Amyloid \u03b2 peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    29, 2566\u20102582 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-265678","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T22:52:23Z","timestamp":1426027943000},"page":"2566-2582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Amyloid\n                    <i>\u03b2<\/i>\n                    peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway"],"prefix":"10.1096","volume":"29","author":[{"given":"Erika","family":"Cecon","sequence":"first","affiliation":[{"name":"Chronopharmacology Laboratory, Institute of Biosciences University of S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1016, Institut Cochin Paris France"},{"name":"Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8104 Paris France"},{"name":"University Paris Descartes, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1016, Institut Cochin Paris France"},{"name":"Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8104 Paris France"},{"name":"University Paris Descartes, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Mar\u00e7ola","sequence":"additional","affiliation":[{"name":"Chronopharmacology Laboratory, Institute of Biosciences University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A. 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