dc.publisher: BioMed Central og:image: https://images.springer.com/sgw/journals/medium/13024.jpg citation_reference: citation_journal_title=Neuron; citation_title=Tau mutations cause frontotemporal dementias; citation_author=M Goedert; citation_author=RA Crowther; citation_author=MG Spillantini; citation_volume=21; citation_issue=5; citation_publication_date=1998; citation_pages=955-8; citation_doi=10.1016/S0896-6273(00)80615-7; citation_id=CR1; citation_journal_title: Molecular Neurodegeneration og:description:

Molecular Neurodegeneration is an open access, peer-reviewed journal that encompasses all aspects of neurodegeneration research at the molecular and cellular levels.

prism.issn: 1750-1326 prism.number: 1 citation_issn: 1750-1326 dc:title: Tau mutant A152T, a risk factor for FTD/PSP, induces neuronal dysfunction and reduced lifespan independently of aggregation in a C. elegans Tauopathy model | Molecular Neurodegeneration | Full Text Content-Encoding: ISO-8859-1 citation_pdf_url: http://molecularneurodegeneration.biomedcentral.com/track/pdf/10.1186/s13024-016-0096-1?site=molecularneurodegeneration.biomedcentral.com DOI: 10.1186/s13024-016-0096-1 citation_fulltext_world_readable: prism.rightsAgent: reprints@biomedcentral.com citation_author: Ghulam Jeelani Pir dc.date: 2016-04-27 citation_abstract_html_url: http://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-016-0096-1 citation_issue: 1 prism.volume: 11 prism.publicationName: Molecular Neurodegeneration citation_doi: 10.1186/s13024-016-0096-1 dc.title: Tau mutant A152T, a risk factor for FTD/PSP, induces neuronal dysfunction and reduced lifespan independently of aggregation in a C. elegans Tauopathy model prism.url: http://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-016-0096-1 citation_volume: 11 dc.language: En Content-Language: en msapplication-TileImage: /static/images/mstile-144x144.9d93277a.png citation_publication_date: 2016/04/27 msapplication-config: /static/images/favicons/biomedcentral/browserconfig.xml citation_title: Tau mutant A152T, a risk factor for FTD/PSP, induces neuronal dysfunction and reduced lifespan independently of aggregation in a C. elegans Tauopathy model citation_author_institution: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany theme-color: #ffffff citation_publisher: BioMed Central dc.format: text/html citation_date: 2016/04/27 title: Tau mutant A152T, a risk factor for FTD/PSP, induces neuronal dysfunction and reduced lifespan independently of aggregation in a C. elegans Tauopathy model | Molecular Neurodegeneration | Full Text dc.source: Molecular Neurodegeneration 2016 11:1 dc.type: OriginalPaper dc.copyright: 2016 Pir et al. dc.creator: Ghulam Jeelani Pir citation_fulltext_html_url: http://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-016-0096-1 prism.publicationDate: 2016-04-27 Content-Type: text/html; charset=ISO-8859-1 journal_id: 13024 X-Parsed-By: org.apache.tika.parser.DefaultParser dc.description: A certain number of mutations in the Microtubule-Associated Protein Tau (MAPT) gene have been identified in individuals with high risk to develop neurodegenerative diseases, collectively called tauopathies. The mutation A152TMAPT was recently identified in patients diagnosed with frontotemporal spectrum disorders, including Progressive Supranuclear Palsy (PSP), Frontotemporal Dementia (FTD), Corticobasal Degeneration (CBD), and Alzheimer disease (AD). The A152TMAPT mutation is unusual since it lies within the N-terminal region of Tau protein, far outside the repeat domain that is responsible for physiological Tau-microtubule interactions and pathological Tau aggregation. How A152TMAPT causes neurodegeneration remains elusive. To understand the pathological consequences of this mutation, here we present a new Caenorhabditis elegans model expressing the mutant A152TMAPT in neurons. While expression of full-length wild-type human tau (Tauwt, 2N4R) in C. elegans neurons induces a progressive mild uncoordinated locomotion in a dose-dependent manner, mutant tau (TauA152T, 2N4R) induces a severe paralysis accompanied by acute neuronal dysfunction. Mutant TauA152T worms display morphological changes in neurons reminiscent of neuronal aging and a shortened life-span. Moreover, mutant A152T overexpressing neurons show mislocalization of pre-synaptic proteins as well as distorted mitochondrial distribution and trafficking. Strikingly, mutant tau-transgenic worms do not accumulate insoluble tau aggregates, although soluble oligomeric tau was detected. In addition, the full-length A152T-tau remains in a pathological conformation that accounts for its toxicity. Moreover, the N-terminal region of tau is not toxic per se, despite the fact that it harbours the A152T mutation, but requires the C-terminal region including the repeat domain to move into the neuronal processes in order to execute the pathology. In summary, we show that the mutant TauA152T induces neuronal dysfunction, morphological alterations in neurons akin to aging phenotype and reduced life-span independently of aggregation. This comprehensive description of the pathology due to TauA152T opens up multiple possibilities to identify cellular targets involved in the Tau-dependent pathology for a potential therapeutic intervention. og:type: article og:title: Molecular Neurodegeneration prism.doi: 10.1186/s13024-016-0096-1 msapplication-TileColor: #da532c citation_firstpage: 33 X-UA-Compatible: IE=edge prism.startingPage: 33 viewport: width=device-width, initial-scale=1 dc.rightsAgent: reprints@biomedcentral.com dc.identifier: 10.1186/s13024-016-0096-1 prism.section: OriginalPaper dc.subject: Neurosciences og:url: http://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-016-0096-1 prism.copyright: 2016 Pir et al.