{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:59:11Z","timestamp":1782280751490,"version":"3.54.5"},"posted":{"date-parts":[[2024,10,22]]},"group-title":"Neuroscience","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The proteostatic decline in Alzheimer\u2019s disease is well established and improvement in proteostasis could potentially delay cognitive impairment. One emerging entry point to modulate proteostasis is the regulation of nucleo-cytoplasmic partitioning of proteins across the nuclear pore via karyopherins. The nuclear exportin XPO1 is a key regulator of proteostasis by driving the assembly of ribosomes and by modulating the process of autophagy. We recently found that XPO1 inhibitor KPT-330 (Selinexor), an FDA approved drug against multiple myelomas, enhances proteostasis, leading to benefits in models of neurodegenerative diseases in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  and\n                  <jats:italic>Drosophila<\/jats:italic>\n                  . Here, we find that KPT-330 increases autophagy in murine neuronal cells and improves spatial memory performance in a murine model of Alzheimer\u2019s disease (5XFAD). Unexpectedly, general amyloid deposition in several brain regions was significantly increased by KPT-330, but specific regions, especially the thalamus, displayed significantly lower deposition, suggesting that XPO1 inhibition has regional-specific effects on proteostasis and amyloid plaque formation. Altogether, we conclude that XPO1 inhibition can improve cognition via spatially-specific reductions in amyloid deposition.\n                <\/jats:p>","DOI":"10.1101\/2024.10.21.619493","type":"posted-content","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T23:20:11Z","timestamp":1729639211000},"source":"Crossref","is-referenced-by-count":1,"title":["Spatial memory in Alzheimer\u2019s disease 5XFAD mice is enhanced by XPO1 inhibitor KPT-330"],"prefix":"10.64898","author":[{"given":"Shi Quan","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adia","family":"Ouellette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery","family":"McNamara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Alexandrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Acacia","family":"Nawrocik-Madrid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus J.","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett C.","family":"Ginsburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo A.","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8154-141X","authenticated-orcid":false,"given":"Louis R.","family":"Lapierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024102515350997000_2024.10.21.619493v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01858-9"},{"issue":"11","key":"2024102515350997000_2024.10.21.619493v1.2","first-page":"1613","article-title":"The effectiveness and value of aducanumab for Alzheimer\u2019s disease","volume":"27","year":"2021","journal-title":"J Manag Care Spec Pharm"},{"key":"2024102515350997000_2024.10.21.619493v1.3","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1034410"},{"key":"2024102515350997000_2024.10.21.619493v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.03.007"},{"key":"2024102515350997000_2024.10.21.619493v1.5","doi-asserted-by":"crossref","unstructured":"Kirli, K. , et al., A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. 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