• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    The proteome of neurofilament-containing heteroaggregates in blood as source of biomarkers for neurodegeneration 
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • The proteome of neurofilament-containing heteroaggregates in blood as source of biomarkers for neurodegeneration
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • The proteome of neurofilament-containing heteroaggregates in blood as source of biomarkers for neurodegeneration
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    The proteome of neurofilament-containing heteroaggregates in blood as source of biomarkers for neurodegeneration

    View/Open
    PhD Thesis (7.655Mb)
    Publisher
    Queen Mary University of London
    Metadata
    Show full item record
    Abstract
    The lack of effective disease-modifying treatments and of means to achieve an early diagnosis strongly support the search for reliable neurochemical biomarkers in neurological conditions like Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder. In ALS, the accumulation of protein aggregates containing neurofilaments (Nf), the building blocks of axons, leads to motor neuron death. Here we investigate the presence of neurofilaments (Nf) in protein aggregates in blood, studying a hallmark of neurodegeneration systemically. We explore the hypothesis that these circulating protein assemblies may function as biomarkers for neurodegeneration in accessible biofluids, which may have future application in clinical practice. In this thesis, I developed a protocol based on ultracentrifugation for the enrichment of protein aggregates from blood and confirmed their enrichment in Nf. Using Mass Spectrometry (MS)-based proteomics, I have obtained data on the protein composition and functional relevance of Nf-Containing Hetero-aggregates (NCHs) in plasma samples from ALS patients, healthy controls (HC) and from ALS brains. I have then applied quantitative proteomics analysis using a TMTcalibrator™ workflow on plasma samples from ALS patients and HC using brain tissue as an internal calibrator. Additional experiments were undertaken to evaluate NCHs resistance to proteases digestion and to characterise the specific conformation of these macromolecular structures by Transmission Electron Microscopy (TEM). Our fluid-brain tissue investigation using a multi-modal approach suggests that NCHs may represent a systemic readout of biochemical changes identified in neurodegenerative brain pathology and suggest that they may acquire altered biochemical properties like protease resistance. The changes in NCHs identified in ALS compared to HC are a promising biological substrate for the future development of next generation biomarkers of neurodegeneration.
    Authors
    Adiutori, Rocco
    URI
    https://qmro.qmul.ac.uk/xmlui/handle/123456789/56853
    Collections
    • Theses [3593]
    Copyright statements
    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.