Principal Investigators

    Dr F Giorgini


    University of Leicester

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    Targeting Parkin and Mitochondrial Dynamics in Huntington's disease

    Source of funding information


    Total sum awarded (Euro)

    € 590,489

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Huntington's disease


    Research Abstract

    Huntington’s disease (HD) is an incurable, fatal neurodegenerative disorder caused by the expansion of a polyglutamine tract in the huntingtin (HTT) protein. This mutation causes HTT to misfold and aggregate, leading to widespread dysfunction and death of vulnerable neurons. As with several other neurodegenerative disorders, the pathogenesis of HD has been closely linked with mitochondrial dysfunction, which includes alterations in mitochondrial dynamics (e.g. increased mitochondrial fragmentation). In preliminary studies we have recently found that the Parkinson’s-linked protein parkin alleviates several disease phenotypes in HD flies when overexpressed. Parkin plays a role in clearance of damaged mitochondria (mitophagy), via modulation of mitochondrial dynamics. Here we propose to further investigate the mechanisms underlying parkin protection in HD fruit flies and a PC12 cell model, and also explore the role of mitochondrial dynamics and mitophagy in pathogenesis of this disorder. We will use genetic approaches to modulate parkin expression in HD models – as well as related proteins (e.g. PINK1, Mfn, Opa1, Drp1) – and ascertain the influence upon mitochondrial phenotypes (e.g. mitochondrial morphology, mitochondrial respiration). Relatedly, as parkin has been found to participate in protein degradation and autophagy of aggregated molecules and reduce proteotoxicity, we will also explore the relationship between parkin and HTT. In total, this work will explore the protective role of parkin in HD, and interrogate mitophagy and mitochondrial dynamics in this disorder. These studies may ultimately contribute to therapeutic strategies for HD.

    Lay Summary

    Further information available at:

Types: Investments > €500k
Member States: United Kingdom
Diseases: Huntington's disease
Years: 2016
Database Categories: N/A
Database Tags: N/A

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