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Elevated MARK2-Depe...
Elevated MARK2-Dependent Phosphorylation of Tau in Alzheimer's Disease
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- Gu, Gucci Jijuan, 1984- (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab,Prof. Ulf Landegren
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- Wu, Di (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab,Prof. Ulf Landegren
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- Lund, Harald (author)
- Karolinska Institutet
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- Sunnemark, Dan (author)
- Dept. of Neuroscience, iMed, CNS and Pain Södertälje, AstraZeneca Research and Development
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- Kvist, Alexander (author)
- Antibody Generation Group, Discovery Sciences, iMed, AstraZeneca Research and Development
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- Milner, Roy (author)
- Antibody Generation Group, Discovery Sciences, iMed, AstraZeneca Research and Development
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- Eckersley, Sonia (author)
- Antibody Generation Group, Discovery Sciences, iMed, AstraZeneca Research and Development
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- Nilsson, Lars (author)
- Uppsala universitet,Geriatrik
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- Agerman, Karin (author)
- Dept. of Neuroscience, iMed, CNS and Pain Södertälje, AstraZeneca Research and Development
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- Landegren, Ulf (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Kamali‐Moghaddam, Masood (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2013
- 2013
- English.
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:3, s. 699-713
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Subject headings
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- The appearance of neurofibrillary tangles (NFT), one of the major hallmarks of Alzheimer's disease (AD), is most likely caused by inappropriate phosphorylation and/or dephosphorylation of tau, eventually leading to the accumulation of NFTs. Enhanced phosphorylation of tau on Ser(262) is detected early in the course of the disease and may have a role in the formation of tangles. Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). Furthermore, we observed elevated interactions between MARK2 and tau in post-mortem human AD brains, compared to samples from non-demented elderly controls. Our results from transfected cells demonstrate a specific interaction between MARK2 and tau, as well as MARK2-dependent phosphorylation of tau at Ser(262). Furthermore, the elevated interactions between MARK2 and tau in AD brain sections suggests that MARK2 may play an important role in early phosphorylation of tau in AD, possibly qualifying as a therapeutic target for intervention to prevent disease progression.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Alzheimer's disease
- MARK
- phosphorylation
- proximity ligation assay
- tau
Publication and Content Type
- ref (subject category)
- art (subject category)
- kfu (subject category)
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- By the author/editor
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Gu, Gucci Jijuan ...
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Wu, Di
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Lund, Harald
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Sunnemark, Dan
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Kvist, Alexander
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Milner, Roy
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show more...
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Eckersley, Sonia
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Nilsson, Lars
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Agerman, Karin
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Landegren, Ulf
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Kamali‐Moghaddam ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Journal of Alzhe ...
- By the university
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Uppsala University
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Karolinska Institutet