Kinase activities increase during the development of tauopathy in htau mice
Open accessAbstract
Hyperphosphorylated tau aggregates are the core constituent of neurofibrillary tangles. Recent research has shown a division between the presence of tangles, neurodegeneration and subsequent memory impairment, raising the possibility that an earlier pre‐aggregated form of tau may be toxic. To gain further insight into the relationship between abnormal forms of tau, we have analyzed pathological changes in tau during tauopathy development in tangle‐forming transgenic mice. In addition, we have quantified changes in the endogenous levels of a panel of protein kinases. We show progressive increases in aggregated tau and disease‐specific conformational change, with hyperphosphorylation occurring in an age‐dependent manner at specific sites. There were significant correlations between specific phosphorylation changes and amounts of aggregated tau and and abnormal tau conformations. Of the protein kinases tested, we found increases in phosphorylated (activated) p38 and the cyclin‐dependent kinase‐5 neuronal activators, p35 and p25, with aging, in the htau line, but not in non‐tangle‐forming control mice. Changes in tau kinases correlated with the amount of tau present in abnormal conformations and with insoluble tau in htau mice. These data suggest that cdk5 and p38 may be associated with pathological changes in wild‐type human tau during the progressive development of tauopathy.
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Elevated p38 activity is found in brains from patients with tauopathies and in transgenic AD mice models expressing human tau or mutant APP, both of which correlate with tau aggregation.
“Elevated p38 activity is found in brains from patients with tauopathies (145–147) and in transgenic AD mice models expressing human tau (148–150) or mutant APP (151), both of which correlate with tau aggregation.”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [149]
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BackgroundResultInfluentialReactivating Kinase/p38 Phosphorylates τ Protein In Vitro
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Retracted
- Authors
- Kelleher, I., Garwood, C., Hanger, D. P., Anderton, B. H., & Noble, W.
- Affiliations
- King's College London (GB)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-08-27
- Volume
- 103
- Issue
- 6
- Pages
- 2256-2267
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2088533926
- Cited by
- 78
- References
- 3
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 5 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 2 · 2012: 6
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tauopathy, tau hyperphosphorylation, protein kinases, cyclin-dependent kinase 5, p38 MAPK, neurofibrillary tangles, tau aggregation, neurodegeneration, memory impairment
- MeSH terms
- Aging, Animals, Brain, Disease Models, Animal, Enzyme Activation, Nerve Tissue Proteins, Phosphorylation, Phosphotransferases, Protein Conformation, Protein Kinases, Up-Regulation, Neurofibrillary Tangles, tau Proteins, Mice, Knockout, Tauopathies, p38 Mitogen-Activated Protein Kinases, Cyclin-Dependent Kinase 5, Mice
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