Genetic factors and analysis of protein misfolding in vivo

Mats Holmberg

    Research output: ThesisThesis fully internal (DIV)

    491 Downloads (Pure)

    Abstract

    Alzheimer’s, Huntington’s and Parkinson’s disease belong to a group of disorders caused by misfolded proteins that are known to stick together in a specific manner forming long fibrils made up of thousands of individual proteins. These fibrils are known as amyloids. It is still unclear which part of the process of aggregation is harmful, and it is even possible that the amyloid is beneficial to the cell because it hides these proteins. In this thesis we identify a protein we have called Modifier of aggregation 4 (MOAG-4), which strongly promotes the formation of these protein aggregates. It affects several amyloid forming proteins but does not appear to act on other proteins that form aggregates in a more disordered fashion. MOAG-4 appears to work independently of other processes that protect cells against protein misfolding. MOAG-4 may help to answer questions about amyloid formation in the cell or can be further explored as a target for therapeutic intervention in neurodegenerative disorders. This thesis also describes two methods useful in the field of protein misfolding. The first one describes an efficient way to screen for protein modification and aggregation. The second method deals with the production of purified proteins which can be used to analyse the behaviour of proteins outside the cell. The strength of both methods lies in their speed and effectiveness.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Nollen, Ellen, Supervisor
    • Mulder, F. (Frans), Co-supervisor, External person
    • Andréasson, (C.) Claes, Co-supervisor, External person
    • van Haastert, Peter, Assessment committee
    • Kampinga, Harrie, Assessment committee
    • Slotboom, Dirk, Assessment committee
    Award date9-Sep-2015
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-90-367-8035-3
    Electronic ISBNs978-90-367-8034-6
    Publication statusPublished - 2015

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