BRADFORD SCHOLARS

    • Sign in
    View Item 
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Bradford ScholarsCommunitiesAuthorsTitlesSubjectsPublication DateThis CollectionAuthorsTitlesSubjectsPublication Date

    My Account

    Sign in

    HELP

    Bradford Scholars FAQsCopyright Fact SheetPolicies Fact SheetDeposit Terms and ConditionsDigital Preservation Policy

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Publication date
    2010
    Author
    Kickstein, E.
    Krauss, S.
    Thornhill, P.
    Rutschow, D.
    Zeller, R.
    Sharkey, J.
    Williamson, Ritchie
    Fuchs, M.
    Kohler, A.
    Glossmann, H.
    Schneider, R.
    Sutherland, C.
    Schweiger, S.
    Show allShow less
    Keyword
    Adenylate Kinase; Metabolism
    ; Alzheimer Disease; Pathology; Physiopathology
    ; Animals
    ; Cells; Cultured
    ; Enzyme Inhibitors; Pharmacology
    ; Epitopes
    ; HeLa cells
    ; Humans
    ; Hypoglycemic agents
    ; Metformin
    ; Mice
    ; Transgenic
    ; Multiprotein complexes
    ; Neurofibrillary Tangles
    ; Neurons; Cytology
    ; Okadaic acid
    ; Phosphorylation
    ; Protein Phosphatase 2
    ; Proteins
    ; Signal Transduction; Drug effects
    ; TOR Serine-Threonine Kinases
    ; Tau Proteins
    ; REF 2014
    Show allShow less
    
    Metadata
    Show full item record
    Abstract
    Hyperphosphorylated tau plays an important role in the formation of neurofibrillary tangles in brains of patients with Alzheimer's disease (AD) and related tauopathies and is a crucial factor in the pathogenesis of these disorders. Though diverse kinases have been implicated in tau phosphorylation, protein phosphatase 2A (PP2A) seems to be the major tau phosphatase. Using murine primary neurons from wild-type and human tau transgenic mice, we show that the antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation at PP2A-dependent epitopes in vitro and in vivo. This tau dephosphorylating potency can be blocked entirely by the PP2A inhibitors okadaic acid and fostriecin, confirming that PP2A is an important mediator of the observed effects. Surprisingly, metformin effects on PP2A activity and tau phosphorylation seem to be independent of AMPK activation, because in our experiments (i) metformin induces PP2A activity before and at lower levels than AMPK activity and (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at the sites analyzed. Affinity chromatography and immunoprecipitation experiments together with PP2A activity assays indicate that metformin interferes with the association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4 protein complex, which regulates the degradation of PP2Ac and thereby influences PP2A activity. In summary, our data suggest a potential beneficial role of biguanides such as metformin in the prophylaxis and/or therapy of AD.
    URI
    http://hdl.handle.net/10454/6051
    Citation
    Kickstein E, Krauss S, Thornhill P et al (2010) Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proceedings of the National Academy of Sciences of the United States of America. 107(50): 21830-21835.
    Link to publisher’s version
    http://dx.doi.org/10.1073/pnas.0912793107
    Type
    Article
    Collections
    Life Sciences Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.