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Tau Silencing by si...
Tau Silencing by siRNA in the P301S Mouse Model of Tauopathy
- Article/chapterEnglish2014
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Bentham Science Publishers Ltd.2014
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LIBRIS-ID:oai:gup.ub.gu.se/205885
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https://gup.ub.gu.se/publication/205885URI
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https://doi.org/10.2174/156652321405140926160602DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Suppression of tau protein expression has been shown to improve behavioral deficits in mouse models of tauopathies, offering an attractive therapeutic approach. Experimentally this had been achieved by switching off the promoters controlling the transgenic human tau gene (MAPT), which is not possible in human patients. The aim of the present study was therefore to evaluate the effectiveness of small interfering RNAs (siRNAs) and their cerebral delivery to suppress human tau expression in vivo, which might be a therapeutic option for human tauopathies. We used primary cortical neurons of transgenic mice expressing P301S-mutated human tau and Lund human mesencephalic (LUHMES) cells to validate the suppressive effect of siRNA in vitro. For measuring the effect in vivo, we stereotactically injected siRNA into the brains of P301S mice to reveal the suppression of tau by immunochemistry (AT180, MC1, and CP13 antibodies). We found that the Accell((TM)) SMART pool siRNA against MAPT can effectively suppress tau expression in vitro and in vivo without a specific delivery agent. The siRNA showed a moderate distribution in the hippocampus of mice after single injection. NeuN, GFAP, Iba-1, MHC II immunoreactivities and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed neither signs of neurotoxicity or neuroinflammation nor apoptosis when MAPT siRNA is present in the hippocampus. Our data suggest that siRNA against MAPT can serve as a potential tool for gene therapy in tauopathies.
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Rosler, T. W.
(author)
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Carlsson, Thomas,1977Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xcatho
(author)
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de Andrade, A.
(author)
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Fiala, O.
(author)
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Hollerhage, M.
(author)
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Oertel, W. H.
(author)
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Goedert, M.
(author)
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Aigner, A.
(author)
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Hoglinger, G. U.
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för farmakologi
(creator_code:org_t)
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In:Current Gene Therapy: Bentham Science Publishers Ltd.14:5, s. 343-3511566-5232
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Xu, H.
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Rosler, T. W.
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Carlsson, Thomas ...
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de Andrade, A.
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Fiala, O.
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Hollerhage, M.
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Oertel, W. H.
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Goedert, M.
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Aigner, A.
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Hoglinger, G. U.
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- MEDICAL AND HEALTH SCIENCES
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Current Gene The ...
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University of Gothenburg