Lakehead University Library Logo
    • Login
    View Item 
    •   Knowledge Commons
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations from 2009
    • View Item
    •   Knowledge Commons
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations from 2009
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    quick search

    Browse

    All of Knowledge CommonsCommunities & CollectionsBy Issue DateAuthorTitleSubjectDisciplineAdvisorCommittee MemberThis CollectionBy Issue DateAuthorTitleSubjectDisciplineAdvisorCommittee Member

    My Account

    Login

    Statistics

    View Usage Statistics

    The development of molecular probes for the in vitro and in vivo study of glucocerebrosidase

    Thumbnail

    View/Open

    TesolinD2017m-1b.pdf (5.454Mb)

    Date

    2017

    Author

    Tesolin, Daniel

    Degree

    Master of Science

    Discipline

    Chemistry

    Subject

    Glucocerebrosidase (GCase)
    Gaucher Disease
    Fluorescent derivatives
    Radioactive derivatives
    Enzyme kinetics
    Radiochemistry

    Metadata

    Show full item record

    Abstract

    Parkinson’s Disease (PD) is one of the most common neurodegenerative diseases in the world. Despite its prevalence, the disease is difficult to diagnose early with the vast majority of individuals already having significant neuronal death prior to therapeutic intervention. PD is characterized by the lysosome’s unusual inability to dispose of α-synuclein in areas of the brain that primarily control motor function. Recently, studies have shown that in post-mortem brain samples from suspected PD patients, there is a deficiency in the activity of the lysosomal enzyme glucocerebrosidase (GCase). GCase is a retaining β-glucosidase that hydrolyzes glucosylceramide in the lysosomes of normal cells. Interestingly, deficiency in enzyme activity was found in both early or late stages of the disease suggesting that GCase could be a biomarker of early PD. To validate GCase as a potential biomarker this thesis focuses on the development of molecular probes for the detection of GCase activity in biological systems. Recently the Phenix lab has developed a class of N-alkylated conduritol aziridines that were shown to be potent and selective irreversible inhibitors of GCase in vitro. A new synthesis pathway has been developed to synthesize these compounds more efficiently and which can be adaptable for producing fluorescent derivatives for in vitro imaging and radioactive derivatives for in vivo imaging. Two new fluorescent derivatives have been developed as well two fluorinated derivatives for future radiolabelling. The development of techniques to radiolabel these compounds is shown in this work. Future work will be done to optimize radiolabelling and test these molecular probes for imaging GCase in biologically relevant systems to validate it as a biomarker for PD.

    URI

    http://knowledgecommons.lakeheadu.ca/handle/2453/4222

    Collections

    • Electronic Theses and Dissertations from 2009

    Lakehead University Library
    Contact Us | Send Feedback

     


    Lakehead University Library
    Contact Us | Send Feedback