{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:31:18Z","timestamp":1779125478561,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T00:00:00Z","timestamp":1152489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Early onset familial Alzheimer's disease (FAD) is linked to autosomal dominant mutations in the amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2) genes. These are critical mediators of total amyloid \u03b2\u2010peptide (A\u03b2) production, inducing cell death through uncertain mechanisms. Tauroursodeoxycholic acid (TUDCA) modulates exogenous A\u03b2\u2010induced apoptosis by interfering with E2F\u20101\/p53\/Bax. Here, we used mouse neuroblastoma cells that express either wild\u2010type APP, APP with the Swedish mutation (APPswe), or double\u2010mutated human APP and PS1 (APPswe\/\u0394E9), all exhibiting increased A\u03b2 production and aggregation. Cell viability was decreased in APPswe and APPswe\/\u0394E9 but was partially reversed by z\u2010VAD.fmk. Nuclear fragmentation and caspase 2, 6 and 8 activation were also readily detected. TUDCA reduced nuclear fragmentation as well as caspase 2 and 6, but not caspase 8 activities. p53 activity, and Bcl\u20102 and Bax changes, were also modulated by TUDCA. Overexpression of p53, but not mutant p53, in wild\u2010type and mutant neuroblastoma cells was sufficient to induce apoptosis, which, in turn, was reduced by TUDCA. In addition, inhibition of the phosphatidylinositide 3\u2032\u2010OH kinase pathway reduced TUDCA protection against p53\u2010induced apoptosis. In conclusion, FAD mutations are associated with the activation of classical apoptotic pathways. TUDCA reduces p53\u2010induced apoptosis and modulates expression of Bcl\u20102 family.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.04007.x","type":"journal-article","created":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T14:23:30Z","timestamp":1152541410000},"page":"1610-1618","source":"Crossref","is-referenced-by-count":55,"title":["Tauroursodeoxycholic acid modulates p53\u2010mediated apoptosis in Alzheimer's disease mutant neuroblastoma cells"],"prefix":"10.1111","volume":"98","author":[{"given":"Rita M.","family":"Ramalho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro M.","family":"Borralho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui E.","family":"Castro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Sol\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford J.","family":"Steer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cec\u00edlia M. 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