{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:54:49Z","timestamp":1779148489771,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102017\u201003904"],"award-info":[{"award-number":["RGPIN\u20102017\u201003904"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brain\u2010derived neurotrophic factor (BDNF) content and signaling has been identified as one potential regulator of amyloid precursor protein (APP) processing. Recently published work has demonstrated that BDNF reduces BACE1 activity while also elevating the inhibition of GSK3\u03b2 in the prefrontal cortex of male C57BL\/6J mice. These results provide evidence that BDNF alters APP processing by reducing BACE1 activity, which may act through GSK3\u03b2 inhibition. The purpose of this study was to further explore the role of GSK3\u03b2 in BDNF\u2010induced regulation on BACE1 activity. We utilized a cell culture and an in\u00a0vitro activity assay model to pharmacologically target BDNF and GSK3\u03b2 signaling to confirm its involvement in the BDNF response. Treatment of differentiated SH\u2010SY5Y neuronal cells with 75\u2009ng\/mL BDNF resulted in elevated pTrkB content, pAkt content, pGSK3\u03b2 content, and reduced BACE1 activity. An in\u00a0vitro BACE1 activity assay utilizing mouse prefrontal cortex (<jats:italic>n<\/jats:italic>\u2009=\u20096\/group) supplemented with BDNF, BDNF + ANA12 (Trkb antagonist), or BDNF + wortmannin (Akt inhibitor) demonstrated that BDNF reduced BACE1 activity; however, in the presence of TrkB or Akt inhibition, this effect was abolished. An in\u00a0vitro ADAM10 activity assay utilizing mouse prefrontal cortex (<jats:italic>n<\/jats:italic>\u2009=\u20096\/group) supplemented with BDNF, BDNF + ANA12 (Trkb antagonist), or BDNF + wortmannin (Akt inhibitor) demonstrated that BDNF did not alter ADAM10 activity. However, inhibiting BDNF signaling reduced ADAM10 activity. Collectively these studies suggest that GSK3\u03b2 inhibition may be necessary for BDNF\u2010induced reductions in BACE1 activity. These findings will allow for the optimization of future therapeutic strategies by selectively targeting TrkB activation and GSK3\u03b2 inhibition.<\/jats:p>","DOI":"10.14814\/phy2.70001","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T05:05:38Z","timestamp":1724130338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Examination of Akt and <scp>GSK3\u03b2<\/scp> in <scp>BDNF<\/scp>\u2010mediated reductions in <scp>BACE1<\/scp> activity in neuronal cells"],"prefix":"10.14814","volume":"12","author":[{"given":"B. J.","family":"Baranowski","sequence":"first","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. J.","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. A.","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Brock University  St. Catharines Ontario Canada"},{"name":"Centre for Neuroscience Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-2658","authenticated-orcid":false,"given":"R.E.K.","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"},{"name":"Centre for Neuroscience Brock University  St. Catharines Ontario 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