CORDIS
EU research results

CORDIS

English EN

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

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.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Principal Investigator

Emi Nagoshi (Dr.)

Host institution

UNIVERSITE DE GENEVE

Address

Rue Du General Dufour 24
1211 Geneve

Switzerland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 518 960

Principal Investigator

Emi Nagoshi (Dr.)

Administrative Contact

Alex Waehry (Mr.)

Beneficiaries (2)

Sort alphabetically

Sort by EU Contribution

Expand all

UNIVERSITE DE GENEVE

Switzerland

EU Contribution

€ 1 518 960

UNIVERSITAET BERN

Switzerland

Project information

Grant agreement ID: 311194

Status

Closed project

  • Start date

    1 June 2013

  • End date

    31 May 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 518 960

  • EU contribution

    € 1 518 960

Hosted by:

UNIVERSITE DE GENEVE

Switzerland