eprintid: 1436872 rev_number: 49 eprint_status: archive userid: 608 dir: disk0/01/43/68/72 datestamp: 2014-08-07 19:35:05 lastmod: 2021-12-10 01:09:25 status_changed: 2014-08-07 19:35:05 type: article metadata_visibility: show item_issues_count: 0 creators_name: Sofola-Adesakin, O creators_name: Castillo-Quan, JI creators_name: Rallis, C creators_name: Tain, LS creators_name: Bjedov, I creators_name: Rogers, I creators_name: Li, L creators_name: Martinez, P creators_name: Khericha, M creators_name: Cabecinha, M creators_name: Bähler, J creators_name: Partridge, L title: Lithium suppresses Aβ pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: F99 divisions: D12 divisions: B04 divisions: C05 divisions: F42 keywords: Alzheimer's disease, Drosophila, lifespan, lithium, translation note: Copyright © 2014 Sofola-Adesakin, Castillo-Quan, Rallis, Tain, Bjedov, Rogers, Li, Martinez, Khericha, Cabecinha, Bähler and Partridge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. abstract: The greatest risk factor for Alzheimer's disease (AD) is age, and changes in the ageing nervous system are likely contributors to AD pathology. Amyloid beta (Aβ) accumulation, which occurs as a result of the amyloidogenic processing of amyloid precursor protein (APP), is thought to initiate the pathogenesis of AD, eventually leading to neuronal cell death. Previously, we developed an adult-onset Drosophila model of AD. Mutant Aβ42 accumulation led to increased mortality and neuronal dysfunction in the adult flies. Furthermore, we showed that lithium reduced Aβ42 protein, but not mRNA, and was able to rescue Aβ42-induced toxicity. In the current study, we investigated the mechanism/s by which lithium modulates Aβ42 protein levels and Aβ42 induced toxicity in the fly model. We found that lithium caused a reduction in protein synthesis in Drosophila and hence the level of Aβ42. At both the low and high doses tested, lithium rescued the locomotory defects induced by Aβ42, but it rescued lifespan only at lower doses, suggesting that long-term, high-dose lithium treatment may have induced toxicity. Lithium also down-regulated translation in the fission yeast Schizosaccharomyces pombe associated with increased chronological lifespan. Our data highlight a role for lithium and reduced protein synthesis as potential therapeutic targets for AD pathogenesis. date: 2014 official_url: http://dx.doi.org/10.3389/fnagi.2014.00190 vfaculties: VFLS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_source: PubMed elements_id: 967814 doi: 10.3389/fnagi.2014.00190 lyricists_name: Adesakin, Oyinkansola lyricists_name: Bahler, Jurg lyricists_name: Bjedov, Ivana lyricists_name: Cabecinha, Melissa lyricists_name: Castillo Quan, Jorge lyricists_name: Partridge, Linda lyricists_name: Rallis, Charalampos lyricists_id: OSOFO56 lyricists_id: JBAHL53 lyricists_id: IBJED78 lyricists_id: MCABE07 lyricists_id: JICAS48 lyricists_id: LPART24 lyricists_id: RCHAR53 full_text_status: public publication: Front Aging Neurosci volume: 6 article_number: 190 event_location: Switzerland citation: Sofola-Adesakin, O; Castillo-Quan, JI; Rallis, C; Tain, LS; Bjedov, I; Rogers, I; Li, L; ... Partridge, L; + view all <#> Sofola-Adesakin, O; Castillo-Quan, JI; Rallis, C; Tain, LS; Bjedov, I; Rogers, I; Li, L; Martinez, P; Khericha, M; Cabecinha, M; Bähler, J; Partridge, L; - view fewer <#> (2014) Lithium suppresses Aβ pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease. Front Aging Neurosci , 6 , Article 190. 10.3389/fnagi.2014.00190 <https://doi.org/10.3389/fnagi.2014.00190>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1436872/1/fnagi-06-00190.pdf