Principal Investigators

    Professor Oliver Bandmann


    University of Sheffield

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    Mitochondrial function in sporadic Parkinson's

    Source of funding information

    Parkinson's UK

    Total sum awarded (Euro)

    € 279,692

    Start date of award


    Total duration of award in years



    Research Abstract

    There is strong evidence for mitochondrial dysfunction in at least some subtypes of familial Parkinson’s (f-PD). However, the prevalence and aetiology of mitochondrial dysfunction in the more common sporadic form of Parkinson’s (s-PD) is largely unknown. Pilot data: We have previously described mitochondrial dysfunction in fibroblasts of f-PD patients. We then showed that Rapamycin-mediated activation of 4E-BP rescues mitochondrial function and have identified novel compounds with a dramatic rescue effect on mitochondrial function in parkin-mutant fibroblasts.
    Overall aim: To characterize mitochondrial dysfunction in s-PD, identify the underlying mechanisms and undertake rescue experiments in patient tissue.
    Specific objectives (methods): 1. Assessment of mitochondrial function and morphology in fibroblasts of 100 s-PD patients (High-throughput biochemical and morphological analysis, already established); 2. Exposure of all those s-PD fibroblast cultures with normal baseline mitochondrial function to toxins (rotenone or paraquat with subsequent assessment of mitochondrial function and morphology) to identify patients with increased susceptibility; 3. Quantification of PGC-1alpha mRNA (Q-PCR) and 4E-BP protein levels (Western blots of phosphorylated vs non-phosphorylated 4E-BP); 4. Rescue experiments with Rapamycin and ‘top hits’ from our own compound screen (pre-treatment for 24h at established doses) Patient recruitment: s-PD patients are already being recruited and skin biopsies already being taken as part of the Oxford Monument study.
    Expected outcome: Our study will give a better understanding of the prevalence and underlying causes of mitochondrial impairment in s-PD, provide insight into mechanisms and determine whether mitochondrial rescue compounds efficient in parkin-mutant patient tissue are also effective in s-PD.

    Further information available at:

Types: Investments < €500k
Member States: United Kingdom
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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