Klingebiel, Maria, Dinekov, Maja and Koehler, Christoph (2017). Analysis of ribosomal protein S6 baseline phosphorylation and effect of tau pathology in the murine brain and human hippocampus. Brain Res., 1659. S. 121 - 136. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1872-6240
Full text not available from this repository.Abstract
We examined the distribution pattern of the phosphorylated 40S ribosomal subunit protein S6, a downstream target of the mTOR pathway, in the brains of 24-months-old human tau transgenic pR5 mice, non-transgenic littermates and in human hippocampi. We studied baseline levels of phosphorylated S6 and a possible effect of tau pathology. S6 phosphorylated at Ser235/236 (pS6Ser235/236) or Ser240/244 (pS6Ser240/244) has been used as a read-out of mTOR activity in several studies. The mTOR pathway regulates a wide variety of cellular functions including cell growth, ribosome biosynthesis, translational control and autophagy. Its dysregulation might underlie the neurodegenerative pathology of Alzheimer's disease and other tauopathies. pS6Ser235/236 and pS6Ser240/244 immunoreactivity in the mouse brain were widespread and similar distributed, but intensive pS6Ser235/236 immunoreactivity was more selective, especially highlighting certain brainstem regions. In the human hippocampus mainly granulovacuolar inclusions in neurons displayed pS6Ser235/236 immunoreactivity. In contrast, a considerable number of neurons displayed pS6Ser240/244 immunoreactivity in the cytoplasm without labeling of granulovacuolar inclusions. Except for a tendency of lower numbers of intensely phosphorylated S6 positive neurons in pR5 mice, the pattern of distribution of pS6Ser235/236 and pS6Ser240/244 immunoreactivity was largely unchanged when compared with non-transgenic mice and also when human hippocampi from AD cases and controls were compared. Similar to pR5 mice most neurons with hyper-phosphorylated tau in human hippocampi displayed no or only weak labeling for phosphorylated S6, suggesting that phosphorylated S6 is not especially associated with pathological tau, but is rather a feature of unaffected neurons. (C) 2017 Elsevier B.V. All rights reserved.
Item Type: | Journal Article | ||||||||||||||||
Creators: |
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URN: | urn:nbn:de:hbz:38-236588 | ||||||||||||||||
DOI: | 10.1016/j.brainres.2017.01.016 | ||||||||||||||||
Journal or Publication Title: | Brain Res. | ||||||||||||||||
Volume: | 1659 | ||||||||||||||||
Page Range: | S. 121 - 136 | ||||||||||||||||
Date: | 2017 | ||||||||||||||||
Publisher: | ELSEVIER SCIENCE BV | ||||||||||||||||
Place of Publication: | AMSTERDAM | ||||||||||||||||
ISSN: | 1872-6240 | ||||||||||||||||
Language: | English | ||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||
Subjects: | no entry | ||||||||||||||||
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Refereed: | Yes | ||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/23658 |
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