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Previously, we discovered that EFV activates CYP46A1 and improves behavioral performance in 5XFAD mice, an Alzheimer's disease model. Herein, the unbiased omics and other approaches were used to study 5XFAD mice in the amyloid\u2010decreasing paradigm of CYP46A1 activation by EFV. These approaches revealed increases in the brain levels of postsynaptic density protein 95, gephyrin, synaptophysin, synapsin, glial fibrillary acidic protein, and CYP46A1 and documented altered expression and phosphorylation of 66 genes and 77 proteins, respectively. The data obtained pointed to EFV effects at the synaptic level, plasmin\u2010depended amyloid clearance, inflammation and microglia phenotype, oxidative stress and cellular hypoxia, autophagy and ubiquitin\u2010proteasome systems as well as apoptosis. These effects could be realized in part\n                    <jats:italic>via<\/jats:italic>\n                    changes in the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010, small GTPase, and catenin signaling. A model is proposed, in which CYP46A1\u2010dependent lipid raft rearrangement and subsequent decrease of protein phosphorylation are central in EFV effects and explain behavioral improvements in EFV\u2010treated 5XFAD mice.\u2014Petrov, A. M., Mast, N., Li, Y., Pikuleva, I. A. The key genes, phosphoproteins, processes, and pathways affected by efavirenz\u2010activated CYP46A1 in the amyloid\u2010decreasing paradigm of efavirenz treatment. FASEB J. 33, 8782\u20138798 (2019).\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.201900092r","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T18:55:43Z","timestamp":1557255343000},"page":"8782-8798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The key genes, phosphoproteins, processes, and pathways affected by efavirenz\u2010activated CYP46A1 in the amyloid\u2010decreasing paradigm of efavirenz treatment"],"prefix":"10.1096","volume":"33","author":[{"given":"Alexey M.","family":"Petrov","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Mast","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Pikuleva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9799"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7238"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303415200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32188-X"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200104000-00003"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.532846"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2619-13.2013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00890.2015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/383728a0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.68.033104.152158"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1748"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3312"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.06.051"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600316103"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187168"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8828-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1074\/mcp.R113.029819","article-title":"Spatiotemporal dynamics of phosphorylation in lipid second messenger signaling","volume":"12","author":"Antal C. 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