{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:37:08Z","timestamp":1787567828863,"version":"build-2736575974"},"reference-count":95,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE2018-T1-002-033"],"award-info":[{"award-number":["MOE2018-T1-002-033"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE2017- 21 T3-1-002"],"award-info":[{"award-number":["MOE2017- 21 T3-1-002"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The emergence of A\u03b2 pathology is one of the hallmarks of Alzheimer\u2019s disease (AD), but the mechanisms and impact of A\u03b2 in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of A\u03b2 on NPC function in neurons. Here, we examined NPC and nucleoporin (NUP) distribution and nucleocytoplasmic transport using a mouse model of AD (\n                    <jats:italic>\n                      App\n                      <jats:sup>NL-G-F\/NL-G-F<\/jats:sup>\n                    <\/jats:italic>\n                    ) that expresses A\u03b2 in young animals. Our studies revealed that a time-dependent accumulation of intracellular A\u03b2 corresponded with a reduction of NPCs and NUPs in the nuclear envelope which resulted in the degradation of the permeability barrier and inefficient segregation of nucleocytoplasmic proteins, and active transport. As a result of the NPC dysfunction\n                    <jats:italic>App<\/jats:italic>\n                    KI neurons become more vulnerable to inflammation-induced necroptosis \u2013 a programmed cell death pathway where the core components are activated via phosphorylation through nucleocytoplasmic shutting. Collectively, our data implicates A\u03b2 in progressive impairment of nuclear pore function and further confirms that the protein complex is vulnerable to disruption in various neurodegenerative diseases and is a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.7554\/elife.92069","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T08:25:59Z","timestamp":1706603159000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92069","source":"Crossref","is-referenced-by-count":2,"title":["A\u03b2-driven nuclear pore complex dysfunction alters activation of necroptosis proteins in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-3633","authenticated-orcid":true,"given":"Vibhavari Aysha","family":"Bansal","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02e7b5302","id-type":"ROR","asserted-by":"publisher"}],"name":"Lee Kong Chian School 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Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Norliyana","family":"Zainolabidin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02e7b5302","id-type":"ROR","asserted-by":"publisher"}],"name":"Lee Kong Chian School of Medicine, Nanyang Technological University","place":["Singapore, Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Takaomi","family":"Saido","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04wn7wc95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences","place":["Nagoya, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7170-1512","authenticated-orcid":true,"given":"Toh Hean","family":"Ch'ng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02e7b5302","id-type":"ROR","asserted-by":"publisher"}],"name":"Lee Kong Chian School of Medicine, Nanyang Technological University","place":["Singapore, Singapore"]},{"id":[{"id":"https:\/\/ror.org\/02e7b5302","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Science, Nanyang Technological University","place":["Singapore, 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