Principal Investigators

    Anna Wredenberg


    Karolinska Institute

    Contact information of lead PI



    Title of project or programme

    Molecular characterisation of mitochondrial disease, using Drosophila melanogaster as model system

    Source of funding information

    Ragnar Söderberg Foundation

    Total sum awarded (Euro)

    € 870,511

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders


    Research Abstract

    Alpha-synuclein is known to contribute to the pathogenesis of Parkinson´s disease (PD) through the formation of toxic aggregates, oligomers, that lead to axonal and synaptic pathology and cell death. Degradation of these toxic intermediates is a promising method to reduce neuronal loss. In addition, there is evidence from autopsy studies that increased cellular levels of alfa-synuclein will cause down-regulation of factors involved in the regulation of dopamine neuron survival and function, most notably the transcription factor Nurr1, which regulates key genes for dopaminergic neurotransmission as well as the expression of the GDNF receptor, Ret. This study will be performed in the rat AAV-alfa-synuclein model, developed and established in the host laboratory, which replicates most of the pathophysiological features of PD. The project is based on two working hypotheses: (i) that impaired expression of the Ret receptor, induced by increased cellular levels of alfa-synuclein, will make the affected DA neurons non-responsive to GDNF and thus more vulnerable to the cellular stress induced by alfa-synuclein, and (ii) That the ability of DA neurons to resist to alfa-synuclein toxicity depends on the efficiency of the lysosome/autophagy pathway, and that pharmacological or genetic-based stimulation of its activity may provide a powerful approach to counteract alfa-synuclein induced damage.

    Lay Summary

    Further information available at:

Types: Investments > €500k
Member States: Sweden
Diseases: Parkinson's disease & PD-related disorders
Years: 2016
Database Categories: N/A
Database Tags: N/A

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