Phosphorylated p38MAPK specific antibodies cross‐react with sarkosyl‐insoluble hyperphosphorylated tau proteins
Abstract
Neurofibrillary tangles (NFT) accumulated in Alzheimer's diseases and related disorders contain hyperphosphorylated tau and display immunoreactivity for active forms of various kinases. To understand the role of p38MAPK (mitogen-activated protein kinase) in NFT formation, we have studied a transgenic (Tg) mouse model of tauopathy, JNPL3, that expresses P301L mutant tau, and bigenic mice, TAPP, generated by cross-breeding of JNPL3 with Tg2576 mice. Age-matched non-Tg mice (NTg), wild-type human tau Tg mice (JN25), and Tg2576 mice were used as controls. Phosphorylated p38MAPK (active form) immunoreactivity was consistently located in NFT and granulovaculolar degeneration in JNPL3 and TAPP mice older than 5 months of age. Unphosphorylated/total-p38MAPK was not detectable in spinal cord and brain sections from 2- to 11-month-old mice, even though JNPL3 mice, but not controls had an age-dependent increase of total-p38MAPK by western blotting. Spinal cord/brain extracts from mice and human with tauopathy were demonstrated to have insignificant amount of active-p38MAPK. However, they contained antiactive-p38MAPK cross-reactive proteins insoluble in sarkosyl and similar to phosphorylated tau in size. Consistently, antiactive-p38MAPK immunoprecipitates displayed tau immunoreactivity, but not total-p38MAPK, and antitau immunoprecipitates displayed active-p38MAPK immunoreactivity. Together, the results indicate that the cross-reactivity of antiactive-p38MAPK antibody with phosphorylated…
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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 [148]
Phospho-p38 is found exclusively in cells with NFT or tau aggregates in AD cases, co-localizes with tau aggregates in tauopathic brains, and co-precipitates with insoluble tau in both human cases and transgenic AD mouse models.
“Phospho-p38 is found exclusively in cells with NFT or tau aggregates in AD cases (152,153), co-localizes with tau aggregates in tauopathic brains (145,154) and co-precipitates with insoluble tau in both human cases and transgenic AD mouse models (145,148).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [148]
Cites
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P38 MAP kinase is activated at early stages in Alzheimer's disease brain
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Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
“Phospho-p38 is found exclusively in cells with NFT or tau aggregates in AD cases (152,153), co-localizes with tau aggregates in tauopathic brains (145,154) and co-precipitates with insoluble tau in both human cases and transgenic AD mouse models (145,148).”
Background
- Authors
- Sahara, N., Vega, I. E., Ishizawa, T., Lewis, J., McGowan, E., Hutton, M., Dickson, D., & Yen, S.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- Saitama Medical University (JP)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-06-28
- Volume
- 90
- Issue
- 4
- Pages
- 829-838
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2004274036
- Cited by
- 15
- References
- 4
- Citations by year
- 2024: 1 · 2023: 1 · 2019: 1 · 2018: 1 · 2016: 2 · 2014: 1
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke (F32NS047930)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- p38 MAPK, tau hyperphosphorylation, neurofibrillary tangles, Alzheimer's disease, tauopathy, antibody cross-reactivity, Tg2576 mice
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Antibodies, Antibody Specificity, Brain, Cross Reactions, Disease Models, Animal, Female, Humans, Mice, Transgenic, Neurons, Phosphorylation, Precipitin Tests, Sarcosine, Solubility, Spinal Cord, Blotting, Western, tau Proteins, Mitogen-Activated Protein Kinases, Tauopathies, p38 Mitogen-Activated Protein Kinases, Mice
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