{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:13:51Z","timestamp":1761920031197},"reference-count":0,"publisher":"Portland Press Ltd.","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,1]]},"abstract":"<jats:p>Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are associated with early-onset familial Alzheimer's disease which displays an accelerated deposition of amyloid plaques and neurofibrillary tangles. Presenilins are multi-spanning transmembrane proteins which localize primarily to the endoplasmic reticulum and the Golgi compartments. We have previously demonstrated that PS1 exists as a high-molecular-mass complex that is likely to contain several functional ligands. Potential binding proteins were screened by the yeast two-hybrid system using the cytoplasmically orientated PS1 loop domain which was shown to interact strongly with members of the armadillo family of proteins, including \u03d0-catenin, p0071 and a novel neuron-specific plakophilin-related armadillo protein (NPRAP). Armadillo proteins can have dual functions that encompass the stabilization of cellular junctions\/synapses and the mediation of signal transduction pathways. Our observations suggest that PS1 may contribute to both aspects of armadillo-related pathways involving neurite outgrowth and nuclear translocation of \u03d0-catenin upon activation of the wingless (Wnt) pathway. Alzheimer's disease (AD)-related presenilin mutations exhibit a dominant gain of aberrant function resulting in the prevention of \u03d0-catenin translocation following Wnt signalling. These findings indicate a functional role for PS1 in signalling and suggest that mistrafficking of selected presenilin ligands may be a potential mechanism in the genesis of AD.<\/jats:p>","DOI":"10.1042\/bss0670089","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T19:13:32Z","timestamp":1439234012000},"page":"89-100","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Presenilin function: connections to Alzheimer's disease and signal transduction"],"prefix":"10.1042","volume":"67","author":[{"given":"Paul E.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyne","family":"L\u00e9vesque","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dun-Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard T.J.","family":"Mount","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"},{"name":"Department of Medicine (Neurology), University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Westaway","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"},{"name":"Department of Laboratory of Medicine and Pathobiology,Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"St George-Hyslop","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada"},{"name":"Department of Medicine (Neurology), University of Toronto, Toronto, Ontario M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Society Symposia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsocsymp\/article-pdf\/doi\/10.1042\/bss0670089\/837619\/bss0670089.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsocsymp\/article-pdf\/doi\/10.1042\/bss0670089\/837619\/bss0670089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T08:24:35Z","timestamp":1637051075000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsocsymp\/article\/doi\/10.1042\/bss0670089\/77594\/Presenilin-function-connections-to-Alzheimer-s"}},"subtitle":[],"editor":[{"given":"Cora","family":"O'Neill","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]},{"given":"Brian","family":"Anderton","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2001,2,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1042\/bss0670089","relation":{},"ISSN":["0067-8694","1744-1439"],"issn-type":[{"value":"0067-8694","type":"print"},{"value":"1744-1439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,2,1]]}}}