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Content archived on 2024-05-29

Parkinson's disease: vulnerability of dopaminergic neurons by Pink 1 versus Parkin mutations in mice

Objective

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder in the aging European society. It is characterized by the preferential degeneration of dopamine (DA)-signalling neurons in the midbrain. Autosomal recessive inheritance of par ticularly early manifesting PD with unusually long therapeutic benefit from dopamine substitution has been traced to mutations in the PARK2 (parkin) protein and the PARK6 (Pink1) protein. Analyses of patients' tissue and genetic animal models indicate that anormalities in mitochondrial energy metabolism and in dopaminergic synaptic signalling underlie the neurodegenerative process in PD. We aim to compare PARK2 and PARK6 brain tissue and analyse dopaminergic and mitochondrial markers, in order to define the common pathways and molecules crucial in the initiation of PD.

For this purpose, we will obtain from Madrid the PARK2 exon 3 knock-out mouse mutant which successfully models the first disease stages, and compare it to the PARK6 G309D knock-in mouse mutant newly available in Frankfurt. Brain tissue will be analysed by 2D electrophoresis proteome analysis / Western / HPLC, fetal midbrain neuron cultures will be used for pharmacological studies of neurotransmission and fluorescence microscopy and Western studies of oxidation damage, and animals will undergo pharmacological modulation to study dopaminergic signalling.

This project is also aimed to network European pioneer teams on PARK2 and PARK6 mouse models and pathogenesis, and provide a promising researcher from the neurotransmission-oriented team in Madrid international postdoctoral training geared towards mitochondria and proteome in Frankfurt. The successful completion of this project would define the crucial molecules for the pathogenesis both of PARK6 and PARK2, and thus provide target molecules to develop lab diagnostic tests of PD and to develop preventive therapy approaches.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-5
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Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

KLINIKUM DER JOHANN WOLFGANG GOETHE-UNIVERSITäT / FRANKFURT AM MAIN
EU contribution
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Address


Germany

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Total cost

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