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dc.contributor.authorSealey, MAen
dc.contributor.authorVourkou, Een
dc.contributor.authorCowan, CMen
dc.contributor.authorBossing, Ten
dc.contributor.authorQuraishe, Sen
dc.contributor.authorGrammenoudi, Sen
dc.contributor.authorSkoulakis, EMCen
dc.contributor.authorMudher, Aen
dc.date.accessioned2017-08-07T13:17:50Z
dc.date.available2017-08-07T13:17:50Z
dc.date.issued2017-09en
dc.identifier.urihttp://hdl.handle.net/10026.1/9686
dc.description.abstract

Tau exists as six closely related protein isoforms in the adult human brain. These are generated from alternative splicing of a single mRNA transcript and they differ in the absence or presence of two N-terminal and three or four microtubule binding domains. Typically all six isoforms have been considered functionally similar. However, their differential involvement in particular tauopathies raises the possibility that there may be isoform-specific differences in physiological function and pathological role. To explore this, we have compared the phenotypes induced by the 0N3R and 0N4R isoforms in Drosophila. Expression of the 3R isoform causes more profound axonal transport defects and locomotor impairments, culminating in a shorter lifespan than the 4R isoform. In contrast, the 4R isoform leads to greater neurodegeneration and impairments in learning and memory. Furthermore, the phosphorylation patterns of the two isoforms are distinct, as is their ability to induce oxidative stress. These differences are not consequent to different expression levels and are suggestive of bona fide physiological differences in isoform biology and pathological potential. They may therefore explain isoform-specific mechanisms of tau-toxicity and the differential susceptibility of brain regions to different tauopathies.

en
dc.format.extent74 - 83en
dc.languageengen
dc.language.isoengen
dc.subject3R tauen
dc.subject4R tauen
dc.subjectAlzheimer's diseaseen
dc.subjectDrosophilaen
dc.subjectIsoformsen
dc.subjectTauopathyen
dc.subjectAge Factorsen
dc.subjectAnimalsen
dc.subjectAnimals, Genetically Modifieden
dc.subjectAxonal Transporten
dc.subjectDisease Models, Animalen
dc.subjectDrosophila Proteinsen
dc.subjectDrosophila melanogasteren
dc.subjectFemaleen
dc.subjectHumansen
dc.subjectLarvaen
dc.subjectLearningen
dc.subjectLocomotionen
dc.subjectMaleen
dc.subjectMemoryen
dc.subjectPhenotypeen
dc.subjectPhosphorylationen
dc.subjectProtein Isoformsen
dc.subjectTandem Repeat Sequencesen
dc.subjectTauopathiesen
dc.subjectTranscription Factorsen
dc.subjectVisual Pathwaysen
dc.subjecttau Proteinsen
dc.titleDistinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/28502805en
plymouth.volume105en
plymouth.publication-statusPublisheden
plymouth.journalNeurobiol Disen
dc.identifier.doi10.1016/j.nbd.2017.05.003en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA03 Allied Health Professions, Dentistry, Nursing and Pharmacy
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeUnited Statesen
dcterms.dateAccepted2017-05-10en
dc.identifier.eissn1095-953Xen
dc.rights.embargoperiodNo embargoen
rioxxterms.versionofrecord10.1016/j.nbd.2017.05.003en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-09en
rioxxterms.typeJournal Article/Reviewen
plymouth.oa-locationhttp://www.sciencedirect.com/science/article/pii/S0969996117301067?via=ihuben


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