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Testing the therapeutic potential of doxycycline in a drosophila melanogaster model of Alzheimer disease

2011-12-02Journal article Open access
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dc.contributor.authorCosta, Rita
dc.contributor.authorSperetta, Elena
dc.contributor.authorCrowther, Damian C.
dc.contributor.authorCardoso, Isabel
dc.date.accessioned2021-09-28T07:42:30Z
dc.date.available2021-09-28T07:42:30Z
dc.date.issued2011-12-02
dc.description.abstractTherapies for Alzheimer disease that reduce the production of pathogenic amyloid beta (A beta) peptides have been associated with a range of unwanted effects. For this reason, alternative strategies that promote the clearance of the peptide by preventing its aggregation and deposition in the brain have been favored. In this context we have studied doxycycline, a member of the tetracycline family of antibiotics that has shown neuroprotective effects in a number of models of neurodegenerative disease. We investigated the neuroprotective potential of doxycycline in a Drosophila model of A beta toxicity and sought to correlate any effects with the aggregation state of the peptide. We found that administration of doxycycline to A beta 42-expressing flies did not improve their lifespan but was able to slow the progression of their locomotor deficits. We also measured the rough eye phenotype of transgenic flies expressing the E22G variant of A beta 42 and showed that doxycycline administration partially rescued the toxicity of A beta in the developing eye. We correlated these in vivo effects with in vitro observations using transmission electron microscopy, dynamic light scattering, and thioflavin T binding. We found that doxycycline prevents A beta fibrillization and favors the generation of smaller, non-amyloid structures that were nontoxic as determined by the lack of caspase 3 activation in a neuroblastoma cell line. Our confirmation that doxycycline can prevent amyloid beta toxicity both in vitro and in vivo supports its therapeutic potential in AD.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCosta, R., Speretta, E., Crowther, D. C., & Cardoso, I. (2011). Testing the therapeutic potential of doxycycline in a Drosophila melanogaster model of Alzheimer Disease*. Journal of Biological Chemistry, 286(48), 41647-41655. https://doi.org/https://doi.org/10.1074/jbc.M111.274548pt_PT
dc.identifier.doi10.1074/jbc.M111.274548pt_PT
dc.identifier.issn1083-351X
dc.identifier.urihttp://hdl.handle.net/10400.22/18579
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJBC Papers in Presspt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0021925820872172?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAmyloid beta-peptidept_PT
dc.subjectParkinsons-diseasept_PT
dc.subjectMouse modelpt_PT
dc.subjectA-betapt_PT
dc.subjectHuntingtons-diseasept_PT
dc.subjectLateral-sclerosispt_PT
dc.subjectRat modelpt_PT
dc.subjectIn-vitropt_PT
dc.subjectMinocyclinept_PT
dc.subjectTetracyclinespt_PT
dc.titleTesting the therapeutic potential of doxycycline in a drosophila melanogaster model of Alzheimer diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage41655pt_PT
oaire.citation.startPage41647pt_PT
oaire.citation.titleJournal of Biological Chemistrypt_PT
oaire.citation.volume286pt_PT
person.familyNameCardoso
person.givenNameIsabel
person.identifier991424
person.identifier.ciencia-id961A-34D6-D5B6
person.identifier.orcid0000-0003-2472-7055
person.identifier.ridK-3903-2013
person.identifier.scopus-author-id6701390815
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication9a1ec9bf-1481-4fe9-b272-6da53f7cdd32
relation.isAuthorOfPublication.latestForDiscovery9a1ec9bf-1481-4fe9-b272-6da53f7cdd32

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