Mislocalization of neuronal tau in the absence of tangle pathology in phosphomutant tau knockin mice
| Autor: | Brian H. Anderton, Laura Sturdee, Michael P. Coleman, Jean Pierre Brion, Diane P. Hanger, Jonathan Gilley, Teresa Rodriguez-Martin, Amy M. Pooler, Kunie Ando, Anjan Seereeram |
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| Přispěvatelé: | Coleman, Michael [0000-0002-9354-532X], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging Pathology medicine.medical_specialty Hyperphosphorylation Neuroscience(all) Tau protein Clinical Neurology tau Proteins Knockin mouse Protein Aggregation Pathological Tangle Serine 03 medical and health sciences Microtubule mental disorders medicine Animals Humans Phosphorylation Phosphomimetic Neurons biology Chemistry General Neuroscience Glutamate receptor Sciences bio-médicales et agricoles Phosphodefective medicine.disease Mice Mutant Strains 3. Good health Ageing Tauopathy 030104 developmental biology Tauopathies biology.protein Neurology (clinical) Tau Geriatrics and Gerontology Neuroscience Developmental Biology |
| Zdroj: | Neurobiology of aging, 39 Gilley, J, Ando, K, Seereeram, A, Rodríguez-Martín, T, Pooler, A M, Sturdee, L, Anderton, B H, Brion, J-P, Hanger, D P & Coleman, M P 2016, ' Mislocalization of neuronal tau in the absence of tangle pathology in phosphomutant tau knockin mice ', Neurobiology of Aging, vol. 39, pp. 1-18 . https://doi.org/10.1016/j.neurobiolaging.2015.11.028 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2015.11.028 |
| Popis: | Hyperphosphorylation and fibrillar aggregation of the microtubule-associated protein tau are key features of Alzheimer's disease and other tauopathies. To investigate the involvement of tau phosphorylation in the pathological process, we generated a pair of complementary phosphomutant tau knockin mouse lines. One exclusively expresses phosphomimetic tau with 18 glutamate substitutions at serine and/or threonine residues in the proline-rich and first microtubule-binding domains to model hyperphosphorylation, whereas its phosphodefective counterpart has matched alanine substitutions. Consistent with expected effects of genuine phosphorylation, association of the phosphomimetic tau with microtubules and neuronal membranes is severely disrupted in vivo, whereas the phosphodefective mutations have more limited or no effect. Surprisingly, however, age-related mislocalization of tau is evident in both lines, although redistribution appears more widespread and more pronounced in the phosphomimetic tau knockin. Despite these changes, we found no biochemical or immunohistological evidence of pathological tau aggregation in mice of either line up to at least 2 years of age. These findings raise important questions about the role of tau phosphorylation in driving pathology in human tauopathies. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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