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Role of Individual ...
Role of Individual MARK Isoforms in Phosphorylation of Tau at Ser262 in Alzheimer's Disease
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- Gu, Gucci Jijuan (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Lund, Harald (author)
- Karolinska Institutet
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- Wu, Di (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Blokzijl, Andries (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Classon, Christina (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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von Euler, Gabriel (author)
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- Landegren, Ulf (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Sunnemark, Dan (author)
- Karolinska Institutet
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- Kamali-Moghaddam, Masood (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2013-05-12
- 2013
- English.
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In: Neuromolecular medicine. - : Springer. - 1535-1084 .- 1559-1174. ; 15:3, s. 458-469
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The microtubule-affinity regulating kinase (MARK) family consists of four highly conserved members that have been implicated in phosphorylation of tau protein, causing formation of neurofibrillary tangles in Alzheimer’s disease (AD). Understanding of roles by individual MARK isoform in phosphorylating tau has been limited due to lack of antibodies selective for each MARK isoform. In this study, we first applied the proximity ligation assay on cells to select antibodies specific for each MARK isoform. In cells, a CagA peptide specifically and significantly inhibited tau phosphorylation at Ser262 mediated by MARK4 but not other MARK isoforms. We then used these antibodies to study expression levels of MARK isoforms and interactions between tau and individual MARK isoforms in postmortem human brains. We found a strong and significant elevation of MARK4 expression and MARK4–tau interactions in AD brains, correlating with the Braak stages of the disease. These results suggest the MARK4–tau interactions are of functional importance in the progression of AD and the results also identify MARK4 as a promising target for AD therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer's disease
- MARK
- Phosphorylation
- Proximity ligation
- Tau
Publication and Content Type
- ref (subject category)
- art (subject category)
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