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Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer’s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery

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dc.contributor.author Vilella, Antonietta
dc.contributor.author Belletti, Daniela
dc.contributor.author Sauer, Ann Katrin
dc.contributor.author Hagmeyer, Simone
dc.contributor.author Sarowar, Tasnuva
dc.contributor.author Masoni, Martina
dc.contributor.author Stasiak, Natalia
dc.contributor.author Mulvihill, John J.
dc.contributor.author Ruozi, Barbara
dc.contributor.author Forni, Flavio
dc.contributor.author Vandelli, Maria Angela
dc.contributor.author Tosi, Giovanni
dc.contributor.author Zoli, Michele
dc.contributor.author Grabrucker, Andreas M.
dc.date.accessioned 2018-07-09T11:11:45Z
dc.date.issued 2017
dc.identifier.citation Vilella, Antonietta,Belletti, Daniela,Sauer, Ann Katrin,Hagmeyer, Simone,Sarowar, Tasnuva,Masoni, Martina,Stasiak, Natalia,Mulvihill, John J.E.,Ruozi, Barbara,Forni, Flavio,Vandelli, Maria Angela,Tosi, Giovanni,Zoli, Michele,Grabrucker, Andreas M. (2017) 'Reduced plaque size and inflammation in the APP23 mouse model for Alzheimerâ  s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery'. Journal of Trace Elements in Medicine and Biology, . en_US
dc.identifier.issn 0946-672X
dc.identifier.uri http://hdl.handle.net/10344/6946
dc.description peer-reviewed en_US
dc.description.abstract A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has been proposed in Alzheimer’s disease (AD) due to the sequestration of zinc in senile plaques. While an increase in zinc levels may promote the aggregation of amyloid beta (Aβ), increased brain zinc might also be beneficial rescuing some pathological alterations caused by local zinc deficiency. For example, increased Aβ degradation by metalloproteinases, and a reduction in inflammation can be hypothesized. In addition, zinc may allow a stabilization of the number of synapses in AD brains. Thus, to evaluate whether altering zinc-levels within the brain is a promising new target for the prevention and treatment of AD, we employed novel zinc loaded nanoparticles able to deliver zinc into the brain across the blood-brain barrier. We performed in vivo studies using wild type (WT) and APP23 mice to assess plaque load, inflammatory status and synapse loss. Furthermore, we performed behavioral analyses. After chronically injecting these nanoparticles for 14 days, our results show a significant reduction in plaque size and effects on the pro-inflammatory cytokines IL-6 and IL-18. On behavioral level we could not detect negative effects of increased brain zinc levels in APP23 mice and treatment with g7-NP-Zn normalized the observed hyperlocomotion of APP23 mice. Therefore, we conclude that a targeted increase in brain zinc levels may have beneficial effects in AD. en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation COST en_US
dc.relation.ispartofseries Journal of Trace Elements in Medicine and Biology;49, pp. 210-221
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0946672X17308428
dc.relation.uri https://doi.org/10.1016/j.jtemb.2017.12.006
dc.rights This is the author’s version of a work that was accepted for publication in Journal of Trace Elements in Medicine and Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Trace Elements in Medicine and Biology, 2017, 49, pp. 210-221 , https://doi.org/10.1016/j.jtemb.2017.12.006 en_US
dc.subject blood brain barrier en_US
dc.subject Alzheimer en_US
dc.subject drug delivery en_US
dc.subject nanoparticle en_US
dc.subject amyloid en_US
dc.title Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer’s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2018-07-09T10:52:21Z
dc.description.version ACCEPTED
dc.identifier.doi 10.1016/j.jtemb.2017.12.006
dc.contributor.sponsor Evangelisches Studienwerk en_US
dc.relation.projectid PRIN 2010-2011 - protocollo: 2010H834LS_003 en_US
dc.relation.projectid TD1304 en_US
dc.date.embargoEndDate 2018-12-27
dc.embargo.terms 2018-12-27 en_US
dc.rights.accessrights info:eu-repo/semantics/opendAccess en_US
dc.internal.rssid 2737883
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Journal of Trace Elements in Medicine and Biology
dc.description.status peer-reviewed


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