Name of Fellow

    Dr George Tofaris



    Wellcome Trust

    Contact information of fellow


    United Kingdom

    Title of project/programme

    Studies on alpha-synuclein degradation and its relevance to Lewy body disease.

    Source of funding information

    Wellcome Trust

    Total sum awarded (Euro)

    € 994,864

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders


    Cognitive impairment | Dementia | Neurodegen | Parkinson

    Research Abstract

    Parkinsons disease (PD), is a common neurodegenerative disorder without pre-symptomatic diagnosis or cure. Although it is established that an accumulation of alpha-synuclein in neurons contributes to PD pathogenesis, the factors influencing the content of this key protein in cells remain poorly understood. I have recently discovered that the ubiquitin-ligase Nedd4 robustly ubiquitinates alpha-synuclein and promotes its degradation by the endosomal-lysosomal pathway. I hypothesize that (a) impair ed degradation of alpha-synuclein by this pathway contributes to the pathogenesis of PD and (b) this pathway can be targeted for neuroprotection. I have the following specific aims: 1. Study in cell models whether Nedd4 regulates the membrane-bound fraction of alpha-synuclein and whether this process involves further post-translational modifications. 2. Investigate using primary neurons whether Nedd4-mediated alpha-synuclein is a target for neuroprotection. 3. Understand how Nedd4 is re gulated in normal and disease states. 4. Study the anatomical distribution, level of expression and post-translational modification of Nedd4 and other endosomal proteins in PD and control brain tissue.

Types: Fellowships
Member States: United Kingdom
Diseases: Parkinson's disease & PD-related disorders
Years: 2016
Database Categories: N/A
Database Tags: N/A

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