{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:52:27Z","timestamp":1784173947419,"version":"3.55.0"},"reference-count":60,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T00:00:00Z","timestamp":1460419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2016,6,7]]},"abstract":"<jats:p>\n                    Research into Alzheimer\u2019s disease pathology and treatment has often focused on presenilin proteins. These proteins provide the key catalytic activity of the \u03b3-secretase complex in the cleavage of amyloid-\u03b2 precursor protein and resultant amyloid tangle deposition. Over the last 25 years, screening novel drugs to control this aberrant proteolytic activity has yet to identify effective treatments for the disease. In the search for other mechanisms of presenilin pathology, several studies have demonstrated that mammalian presenilin proteins also act in a non-proteolytic role as a scaffold to co-localize key signaling proteins. This role is likely to represent an ancestral presenilin function, as it has been described in genetically distant species including non-mammalian animals, plants, and a simple eukaryotic amoeba\n                    <jats:italic>Dictyostelium<\/jats:italic>\n                    that diverged from the human lineage over a billion years ago. Here, we review the non-catalytic scaffold role of presenilin, from mammalian models to other biomedical models, and include recent insights using\n                    <jats:italic>Dictyostelium,<\/jats:italic>\n                    to suggest that this role may provide an early evolutionary function of presenilin proteins.\n                  <\/jats:p>","DOI":"10.3233\/jad-150940","type":"journal-article","created":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T13:44:32Z","timestamp":1465566272000},"page":"1177-1187","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["Non-Catalytic Roles of Presenilin Throughout Evolution"],"prefix":"10.1177","volume":"52","author":[{"given":"Grant P.","family":"Otto","sequence":"first","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devdutt","family":"Sharma","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin S.B.","family":"Williams","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,4,12]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006304"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638621"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/376775a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80291-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.6.3205"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400897"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.118.3.573"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2583"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/13506120109007356"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi301252r"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2007.01.008"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-101065"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.5.723"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14940"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","unstructured":"De StrooperB SaftigP CraessaertsK VandersticheleH GuhdeG AnnaertW Von FiguraK Van LeuvenF (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. 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