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It is the only one of the top ten causes of death in the\n                    <jats:styled-content style=\"fixed-case\">USA<\/jats:styled-content>\n                    for which prevention strategies have not been developed. Although\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    has traditionally been associated with the deposition of amyloid \u03b2 plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    . An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    . We show here that oral administration of fisetin to\n                    <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content>\n                    swe\/\n                    <jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content>\n                    1d\n                    <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\n                    9 double transgenic\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    mice from 3 to 12\u00a0months of age prevents the development of learning and memory deficits. This correlates with an increase in\n                    <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n                    phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin\u2010dependent kinase 5 (\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    dk5) activator p35 cleavage product, p25, in both control and\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    brains. Elevated levels of p25 relative to p35 cause dysregulation of\n                    <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\n                    dk5 activity leading to neuroinflammation and neurodegeneration. These fisetin\u2010dependent changes correlate with additional anti\u2010inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    mice. Together, these results suggest that fisetin may provide a new approach to the treatment of\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/acel.12185","type":"journal-article","created":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T05:48:56Z","timestamp":1387259336000},"page":"379-390","source":"Crossref","is-referenced-by-count":202,"title":["Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in\n                    <scp>A<\/scp>\n                    lzheimer's disease transgenic mice"],"prefix":"10.1111","volume":"13","author":[{"given":"Antonio","family":"Currais","sequence":"first","affiliation":[{"name":"The Salk Institute for Biological Studies 10010\u00a0N. Torrey Pines Road La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguerite","family":"Prior","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies 10010\u00a0N. Torrey Pines Road La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Dargusch","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies 10010\u00a0N. Torrey Pines Road La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Armando","sequence":"additional","affiliation":[{"name":"Depatment of Medicine University of California at San Diego 9500 Gilman Drive #0601 La Jolla CA 92093\u20100601 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ehren","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies 10010\u00a0N. Torrey Pines Road La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schubert","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies 10010\u00a0N. Torrey Pines Road La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oswald","family":"Quehenberger","sequence":"additional","affiliation":[{"name":"Depatment of Medicine University of California at San Diego 9500 Gilman Drive #0601 La Jolla CA 92093\u20100601 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Maher","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies 10010\u00a0N. 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