| Hyperphosphorylated truncated protein tau induces caspase-3 independent apoptosis-like pathway in the Alzheimer's disease cellular model. | |
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MedLine Citation:
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PMID: 20966551 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neurofibrillary degeneration and neuronal loss represent key pathological hallmarks of Alzheimer's disease (AD). It has been demonstrated that the decrease of total neuronal numbers correlates with the presence of neurofibrillary degeneration in AD brain. In order to unravel the mechanism leading to the cell death in AD, we developed a stably transfected human neuroblastoma cellular model with doxycycline-regulatable expression of AD truncated tau protein (AT tau, 151-391 4R). Cells expressing the longest tau isoform (Tau 40) were used as a control. We found that more than 80% of the total amount of AT tau and Tau 40 were phosphorylated. Strikingly, both AT tau and Tau 40 reduced the metabolic activity of the cells in a time-dependent manner (p < 0.0001) suggesting that tau overexpression slows down cell proliferation. However, AT tau showed significantly higher toxicity than Tau 40 (p < 0.0001), which indicates that truncation leads to a toxic gain of function. The analysis of the type of the cell death revealed the characteristic features of apoptosis such as cell shrinkage, nuclear, and DNA fragmentation. However, we did not find either the activation of executive caspase (caspase-3) or the caspase cleavage products (PARP and fodrin). These results show that posttranslationally modified truncated tau protein induces caspase-3-independent apoptosis-like programmed cell death, a phenomenon we term tauoptosis. |
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Authors:
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Monika Zilkova; Norbert Zilka; Andrej Kovac; Branislav Kovacech; Rostislav Skrabana; Michaela Skrabanova; Michal Novak |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of Alzheimer's disease : JAD Volume: 23 ISSN: 1875-8908 ISO Abbreviation: J. Alzheimers Dis. Publication Date: 2011 |
Date Detail:
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Created Date: 2011-01-13 Completed Date: 2011-05-05 Revised Date: 2011-08-19 |
Medline Journal Info:
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Nlm Unique ID: 9814863 Medline TA: J Alzheimers Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 161-9 Citation Subset: IM |
Affiliation:
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Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic Axon-Neuroscience GmbH, Vienna, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Apoptosis / genetics, physiology* Carrier Proteins / genetics, metabolism Caspase 3 / metabolism* Cell Count Cell Line, Tumor DNA Fragmentation / drug effects Gene Expression / genetics Humans In Situ Nick-End Labeling / methods Microfilament Proteins / genetics, metabolism Mutation / genetics Neuroblastoma Phosphorylation / drug effects, genetics Signal Transduction / drug effects, genetics* Transfection tau Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Microfilament Proteins; 0/fodrin; 0/tau Proteins; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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