Elucidating the Role of Phosphorylation by Polo-like kinases in Modulating Alpha-Synuclein Aggregation and Toxicity in Parkinson's disease and Related Disorders

Project Information

PLKS IN PD

Grant agreement ID: 237688

Project closed

Start date 1 May 2009

End date 30 April 2011

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 180 234,43

EU contribution € 180 234,43

Coordinated by

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland

Objective

Increasing evidence suggest that alpha-synuclein (a-syn) phosphorylation plays an important role in the regulation of a-syn aggregation, Lewy Bodies (LBs) formation and neurotoxicity in Parkinson’s disease (PD) and related synucleopathies. However, the exact kinase(s) responsible for phosphorylating a-syn and the relationships between phosphorylation, a-syn fibrillogenesis, LB formation and cell death have not been fully elucidated. Preliminary data in our Laboratory have pointed out a Polo-Like Kinase family (Plks) as an interesting candidate for a-syn phosphorylation and modulating protein aggregation. To determine the relationship between the phosphorylation of a-syn by Plk family, protein aggregation and neurodegeneration, we plan to use an integrative approach combining in vitro and in vivo approaches. In the in vitro part, we seek to elucidate the role of phosphorylation by Plks in modulating a-syn aggregation in vitro and in primary cell culture. In the in vivo part, we plan to study the possible co-localization of Plks and phosphorylated and unphosphorylated a-syn in LBs inclusions in the brain of parkinsonians patients and animal models of PD. We also seek to evaluate the biochemical and functional consequences of co-delivering Plks and various modified forms of a-syn directly to the rodent brain. This proposal will give us the opportunity to better understand functional consequences of a-syn phosphorylation and mechanisms by which it contributes to neurotoxicity. That will allow us to identify new therapeutic targets of synucleopathies treatment.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.

• natural sciences › biological sciences › neurobiology
• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• medical and health sciences › basic medicine › neurology › parkinson

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Keywords

• Alpha-synuclein
• Polo-Like Kinases
• phosphorylation
• protein aggregation
• synucleopathies

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• FP7-PEOPLE-IEF-2008 - Marie Curie Action: "Intra-European Fellowships for Career Development"

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE

• EU contribution: € 180 234,43
• Address: BATIMENT CE 3316 STATION 1 ; 1015 Lausanne ; Switzerland
• Region: Schweiz/Suisse/Svizzera › Région lémanique › Vaud
• Activity type: Higher or Secondary Education Establishments
• Total cost: No data