Enter a sentence, or cut and paste a paragraph

Refine

Refine

Refine to these subject areas:

  • Select All | Select None

Advanced Filters »

Refine

  • Advanced Filters:

  • to

  • Specific Data Sources:

    All Edit

    Select All  |  Select None

Reset filters

Journals The FASEB Journal September 2009

Bookmark

{alpha}-Synuclein contributes to GSK-3{beta}-catalyzed Tau phosphorylation in Parkinson's disease models

To view this document, you will need to have Adobe Flash Player 10 or above installed.
Please click here to install.

We have shown in the parkinsonism-inducing neurotoxin MPP + /MPTP model that -Synuclein ( -Syn), a presynaptic protein causal in Parkinson’s disease (PD), contributes to hyperphosphorylation of Tau (p-Tau), a protein normally linked to tauopathies, such as Alzheimer’s disease (AD). Here, we investigated the kinase involved and show that the Tau-specific kinase, glycogen synthase kinase 3β (GSK-3β), is robustly activated in various MPP + /MPTP models of Parkinsonism (SH-SY5Y cotransfected cells, mesencephalic neurons, transgenic mice overexpressing -Syn, and postmortem striatum of PD patients). The activation of GSK-3β was absolutely dependent on the presence of -Syn, as indexed by the absence of p-GSK-3β in cells lacking -Syn and in -Syn KO mice. MPP + treatment induced translocation and accumulation of p-GSK-3β in nuclei of SH-SY5Y cells and mesencephalic neurons. Through coimmunoprecipitation (co-IP), we found that -Syn, pSer396/404-Tau, and p-GSK-3β exist as a heterotrimeric complex in SH-SY5Y cells. GSK-3β inhibitors (lithium and TDZD-8) protected against MPP + -induced events in SH-SY5Y cells, preventing cell death and p-GSK-3β formation, by reversing increases in -Syn accumulation and p-Tau formation. These data unveil a previously unappreciated role of -Syn in the induction of p-GSK-3β, and demonstrate the importance of this kinase in the genesis and maintenance of neurodegenerative changes associated with PD.—Duka, T., Duka, V., Joyce, J. N., Sidhu, A. -Synuclein contributes to GSK-3β-catalyzed Tau phosphorylation in Parkinson’s disease models.

To view this document, you will need to have Adobe Flash Player 10 or above installed.
Please click here to install.

This is a preview. The total pages displayed will be limited.

Rent for $0.99 FREE

Login

It seems like you have an account, please login to rent this article

Forgot your password?

Don't have an account yet? Sign up now!

To view the full-text of this article, sign up for a free DeepDyve account below.

A free Basic account also comes with
3 free rentals to help get you started.

It seems like you have an account, please login to rent this article

Just 30 seconds to go! Please check your inbox for a confirmation email to activate your account, then start using your 3 FREE rentals.

Learn more Existing user? Login here

Article Details
Duka, Tetyana; Duka, Valeriy; Joyce, Jeffrey N.; Sidhu, Anita
The FASEB Journal , Volume 23 (9): 2820
Fed of American Socs for Experimental Biology – Sep 1, 2009
More Info

More Like This Article

View All dataSource[]=aspet&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imedpub&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=oxford&dataSource[]=pnas&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=pct

Browse: Subject Areas | Journals | Publishers

Bookmark an Article

To bookmark an article, please log in first, or sign up for a DeepDyve account if you don't already have one.

OK

Subscribe to Journal Email Alerts

To subscribe to email alerts, please log in first, or sign up for a DeepDyve account if you don't already have one.

OK