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Increased tau phosphorylation on mitogen-activated protein kinase consensus sites and cognitive decline in transgenic models for Alzheimer's disease and FTDP-17: evidence for distinct molecular processes underlying tau abnormalities
DC Field | Value | Language |
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dc.contributor.author | Lambourne, Sarah L. | - |
dc.contributor.author | Sellers, Lynda A. | - |
dc.contributor.author | Bush, Toby G. | - |
dc.contributor.author | Choudhury, Shewly K. | - |
dc.contributor.author | Emson, Piers C. | - |
dc.contributor.author | Suh, Yoo-Hun | - |
dc.contributor.author | Wilkinson, Lawrence S. | - |
dc.date.accessioned | 2010-01-07T05:14:52Z | - |
dc.date.available | 2010-01-07T05:14:52Z | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Mol. Cell Biol. 25:278-293 | en |
dc.identifier.issn | 0270-7306 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15601849 | - |
dc.identifier.uri | https://hdl.handle.net/10371/28239 | - |
dc.description.abstract | Abnormal tau phosphorylation occurs in several neurodegenerative disorders, including Alzheimer's disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). Here, we compare mechanisms of tau phosphorylation in mouse models of FTDP-17 and AD. Mice expressing a mutated form of human tau associated with FTDP-17 (tau(V337M)) showed age-related increases in exogenous tau phosphorylation in the absence of increased activation status of a number of kinases known to phosphorylate tau in vitro. In a "combined" model, expressing both tau(V337M) and the familial amyloid precursor protein AD mutation APP(V717I) in a CT100 fragment, age-dependent tau phosphorylation occurred at the same sites and was significantly augmented compared to "single" tau(V337M) mice. These effects were concomitant with increased activation status of mitogen-activated protein kinase (MAPK) family members (extracellular regulated kinases 1 and 2, p38, and c-Jun NH(2)-terminal kinase) but not glycogen synthase kinase-3alphabeta or cyclin-dependent kinase 5. The increase in MAPK activation was a discrete effect of APP(V717I)-CT100 transgene expression as near identical changes were observed in single APP(V717I)-CT100 mice. Age-dependent deficits in memory were also associated with tau(V337M) and APP(V717I)-CT100 expression. The data reveal distinct routes to abnormal tau phosphorylation in models of AD and FTDP-17 and suggest that in AD, tau irregularities may be linked to processing of APP C-terminal fragments via specific effects on MAPK activation status. | en |
dc.language.iso | en | en |
dc.publisher | American Society for Microbiology | en |
dc.subject | Alzheimer Disease/genetics | en |
dc.subject | Amyloid beta-Protein/metabolism | en |
dc.subject | Animals | en |
dc.subject | Blotting, Western | en |
dc.subject | Brain/metabolism | en |
dc.subject | Cell Membrane/metabolism | en |
dc.subject | Cyclin-Dependent Kinase 5 | en |
dc.subject | Cyclin-Dependent Kinases/metabolism | en |
dc.subject | DNA, Complementary/metabolism | en |
dc.subject | Enzyme-Linked Immunosorbent Assay | en |
dc.subject | Glycogen Synthase Kinase 3/metabolism | en |
dc.subject | Glycogen Synthase Kinases/metabolism | en |
dc.subject | Humans | en |
dc.subject | Image Processing, Computer-Assisted | en |
dc.subject | Immunohistochemistry | en |
dc.subject | In Situ Hybridization | en |
dc.subject | Membrane Proteins/chemistry | en |
dc.subject | Mice | en |
dc.subject | Mice, Transgenic | en |
dc.subject | Mutation | en |
dc.subject | Phosphorylation | en |
dc.subject | Prosencephalon/metabolism | en |
dc.subject | Protein Structure, Tertiary | en |
dc.subject | Rhombencephalon/metabolism | en |
dc.subject | Signal Transduction | en |
dc.subject | Time Factors | en |
dc.subject | Transgenes | en |
dc.subject | tau Proteins/*chemistry/metabolism | en |
dc.subject | MAP Kinase Signaling System | - |
dc.title | Increased tau phosphorylation on mitogen-activated protein kinase consensus sites and cognitive decline in transgenic models for Alzheimer's disease and FTDP-17: evidence for distinct molecular processes underlying tau abnormalities | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 서유훈 | - |
dc.identifier.doi | 10.1128/MCB.25.1.278-293.2005 | - |
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