The molecular role of Serf2 in development and misfolded protein aggregation

Esther Stroo

    Research output: ThesisThesis fully internal (DIV)

    477 Downloads (Pure)

    Abstract

    Protein aggregation in the brain is a common hallmark of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. The biological mechanism of protein aggregation remains unresolved. This thesis describes the function of an enhancer of protein aggregation, Serf2, in development and in a model for Alzheimer's disease.
    Loss of Serf2 in mice leads to neonatal death and reduced body weight and size. Pathological analyses reveals less matured lung tissue, and as a result the mice without Serf2 are not able to breath after birth and die. Cells of these mice also grow slower, and show a change in the genes that regulate cell cycle. These findings show that Serf2 is important for embryonic growth and viability, by a direct or indirect role in cell division.
    Serf2 can directly affect protein aggregation of disease proteins in a test tube. To discover if absence of Serf2 has an effect on disease pathology, we deleted Serf2 in the brain of an Alzheimer mouse model. Loss of Serf2 does not affect the Alzheimer pathology quantitatively but appears to change the morphology to more compact and less regular structures. Others have correlated such structural differences to Alzheimer disease severity. Based on our results it is possible that inherited factors like Serf2 drive these changes, which would make them a target to actively redirect disease proteins to more benign lesions.
    More research will be required to determine the consequences of the structural changes for the health of the brain, before Serf2 inhibition can be explored as a therapeutic intervention.
    Translated title of the contributionDe moleculaire rol van Serf2 in ontwikkeling en eiwitaggregatie
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Nollen, Ellen, Supervisor
    • de Bruin, Alain, Supervisor
    • Mallucci, G.R., Assessment committee, External person
    • Verbeek, Dineke, Assessment committee
    • Calkhoven, Cor, Assessment committee
    Award date7-May-2018
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-0568-1
    Electronic ISBNs978-94-034-0567-4
    Publication statusPublished - 2018

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