An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice
| Autor: | Mike Hutton, Hanno Roder, Barbara Monse, Gabriele Hübinger, Cynthia Zehr, Jason L. Eriksen, Nikolaus Plesnila, Sylvie Le Corre, Mei Yue, Heidi Sahagún, Hans Klafki, Eileen McGowan, Jada Lewis, Dennis W. Dickson, Axel Obermeier, Pierfausto Seneci |
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| Rok vydání: | 2006 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Transgene Carbazoles Mice Transgenic tau Proteins Motor Activity chemistry.chemical_compound Mice Internal medicine Physical Conditioning Animal mental disorders Okadaic Acid medicine Animals Transgenes Phosphorylation Multidisciplinary Molecular Structure Kinase Neurofibrillary tangle Okadaic acid Biological Sciences medicine.disease Rats Mice Inbred C57BL Motor Skills Disorders Disease Models Animal Endocrinology chemistry Biochemistry Solubility Female K252a Tauopathy |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 103(25) |
| ISSN: | 0027-8424 |
| Popis: | An orally bioavailable and blood–brain barrier penetrating analog of the kinase inhibitor K252a was able to prevent the typical motor deficits in the tau (P301L) transgenic mouse model (JNPL3) and markedly reduce soluble aggregated hyperphosphorylated tau. However, neurofibrillary tangle counts were not reduced in the successfully treated cohort, suggesting that the main cytotoxic effects of tau are not exerted by neurofibrillary tangles but by lower molecular mass aggregates of tau. Our findings strongly suggest that abnormal tau hyperphosphorylation plays a critical role in the development of tauopathy and suggest a previously undescribed treatment strategy for neurodegenerative diseases involving tau pathology. |
| Databáze: | OpenAIRE |
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