• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Potential Role of Tazarotene-Induced Gene 3 and Transglutaminase 1 in Tauopathies

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Kizilyer_umaryland_0373N_10460.pdf
    Size:
    4.389Mb
    Format:
    PDF
    Download
    Author
    Kizilyer, Yasin
    Advisor
    Eckert, Richard (Richard L.)
    Date
    2013
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    The family of neurodegenerative diseases, called tauopathies, includes Alzheimer's disease, progressive supranuclear palsy, and Pick's disease. These diseases are associated with the formation of tau inclusions and neuronal cell death. Tau inclusions are characterized by the presence of neurofibrillary tangles (NFTs), where protein Tau, a member of microtubule-associated proteins (MAPs), is found to be, hyperphosphorylated and aggregated. The formation of these aggregates leads to microtubule instability and cellular toxicity. There are several lines of evidence that demonstrate this aggregation is due to transglutaminase mediated cross-linking of Tau protein. However, little is known about the mechanism of the hyperphosphorylation, aggregation and tau-associated toxicity. Analysis of brains with tau pathologies showed the colocalized expression of transglutaminase 1 (TG1) and its activator, tazarotene-induced gene 3 (TIG3) in NFTs, suggesting functional relevancy. Hereby, we hypothesized that TIG3 regulates TG1-catalysed cross-linking of Tau, and therefore the formation of Tau inclusions in neurons. To test this hypothesis, neurons differentiated from human embryonic stem cells used to develop an in-vitro tauopathy model. Endogenous expression analyses of TIG3, TG1 and Tau were performed and induction of Tau occlusions via overexpression of TIG3 studied. Results have shown endogenous TIG3 mRNA and protein were expressed in neurons derived from embryonic stem cells. Endogenous TIG3, TG1 and TAU have shown colocalization. Cells overexpressing TIG3 have shown a higher level of colocalization and increased Tau aggregation, which confirmed our hypothesis. The results of this study provide new mechanistic insights into the formation of neurofibrillary tangles and the resulting pathology.
    Description
    University of Maryland, Baltimore. Molecular Medicine. M.S. 2013
    Keyword
    human embryonic stem cells derived neurons
    tau
    tazarotene-induced gene 3
    transglutaminase 1
    Neurofibrillary Tangles
    Tauopathies
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/2979
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    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.