2STEPPARKIN

A novel two-step model for neurodegeneration in Parkinson’s disease

 Coordinatore UNIVERSITE DE GENEVE 

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 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 1˙518˙960 €
 EC contributo 1˙518˙960 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2012-StG_20111109
 Funding Scheme ERC-SG
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-06-01   -   2018-05-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITAET BERN

 Organization address address: Hochschulstrasse 4
city: BERN
postcode: 3012

contact info
Titolo: Ms.
Nome: Maddalena
Cognome: Tognola
Email: send email
Telefono: +41 31 6314809

CH (BERN) beneficiary 0.00
2    UNIVERSITE DE GENEVE

 Organization address address: Rue du General Dufour 24
city: GENEVE
postcode: 1211

contact info
Titolo: Dr.
Nome: Alex
Cognome: Waehry
Email: send email
Telefono: +41 22 379 75 60
Fax: +41 22 379 11 80

CH (GENEVE) hostInstitution 1˙518˙960.00
3    UNIVERSITE DE GENEVE

 Organization address address: Rue du General Dufour 24
city: GENEVE
postcode: 1211

contact info
Titolo: Dr.
Nome: Emi
Cognome: Nagoshi
Email: send email
Telefono: +41 22 379 67 70
Fax: +41 22 379 67 70

CH (GENEVE) hostInstitution 1˙518˙960.00

Mappa


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propagates    neuron    pd    progressive    hypothesis    fer    pathogenesis    underlying    discovery    gene    exhibit    subsequently    da    death    neurons    drosophila    mechanisms    loss    degeneration    cell    model   

 Obiettivo del progetto (Objective)

'Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.'

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