RECYCLING PARKINSON

Synaptic vesicle recycling and Parkinson’s disease

Coordinatore	ACADEMISCH ZIEKENHUIS LEIDEN    more  Organization address address: Albinusdreef 2 city: LEIDEN postcode: 2333 ZA contact info Titolo: Ms. Nome: Karin Cognome: Wibier Email: send email Telefono: 31715269568
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-03-01   -   2017-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	ACADEMISCH ZIEKENHUIS LEIDEN  Organization address address: Albinusdreef 2 city: LEIDEN postcode: 2333 ZA contact info Titolo: Ms. Nome: Karin Cognome: Wibier Email: send email Telefono: 31715269568	NL (LEIDEN)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'The nervous system consists of a complex network of neurons interconnected by chemical synapses. Recycling of neurotransmitter filled vesicles at theses synapses enables neurons to maintain communication during periods of intense activity. There is accumulating evidence that synaptic dysfunction is, at least in part, responsible for common neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s disease. I therefore set out to find genes involved in the synaptic pathogenesis of these diseases by performing a forward genetic screen in Drosophila melanogaster. I isolated more than 86 mutants in a screen for non-canonical vesicle recycling and found that one of the them genetically interacts with the Parkinson’s related gene pink1 in a secondary screen. I mapped this mutation to the Drosophila ortholog of NOA1, a conserved gene encoding a mitochondrial protein whose function remains largely enigmatic. Since both proteins, PINK1 and NOA1 are reported to localize in mitochondria and interact with Complex I of the respiratory chain, I hypothesize that they function in the same pathway. Here, I describe experiments to determine the exact nature of the interaction between Drosophila PINK1 and NOA1 and present plans to examine the molecular function of Drosophila Noa1 at the synapse. In addition, I will further characterize the remaining mutants for interactions with α-Synuclein, a protein known to be involved in Parkinson’s disease. In this way, I will find new components of the vesicle recycling machinery that interact with Parkinson’s disease-related proteins which will not only further our understanding of the mechanisms underlying synapse function, but also identify possible new therapeutic targets for this disease.'