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The continuum between healthy ageing and idiopathic Parkinson Disease within a propagation perspective of inflammation and damage: the search for new diagnostic, prognostic and therapeutic targets

Objective

Ageing is the major risk factor for idiopathic PARKINSON'S DISEASE (PD), the first motor neurodegenerative disorder (in EU 1% in 65+; about 4% in 80+). The most recent conceptualizations of ageing and PD indicate that they share basic mechanisms, e.g. accumulation of senescent cells and propagation phenomena such as inflammaging mirrored in PD by neuro-inflammaging in brain that foster a prion-like spreading of neuronal damage. Thus, to fully understand PD pathogenesis and set up innovative neuro-protective therapies it is mandatory to posit PD within the framework of ageing process. The main goal of PROPAG-AGEING is to identify specific cellular and molecular perturbations deviating from healthy ageing trajectories towards PD. To this aim the project will exploit four large, very informative EXISTING COHORTS where biomaterials are available: i) de novo PD patients (before any therapy) followed longitudinally, including the largest repository of PD patients, i.e. PPMI; ii) centenarians and their offspring (CO) who never showed clinical signs of motor disability; iii) old twins of the Swedish Twin Registry (STR) followed longitudinally for >45 years, assessed for lifestyle and exposure to toxicants, and where incident and prevalent cases of PD discordant twins have been collected, including brains. The most informative sample from these cohorts will be studied in a DISCOVERY PHASE by an integrated set of omics to identify molecular signatures whose results will enter in a VALIDATION PHASE exploiting the four large cohorts, and performing functional in in vitro studies using dopaminergic neurons obtained by PD somatic cells from PD patients and centenarians via iPSC protocol. An added value is that omic data in centenarians and CO are available, and will represent the gold standard of healthy ageing. This approach will allow to identify new molecular profiles for early diagnosis and therapy (identification of druggable targets) of PD and signatures of healthy ageing.

Field of science

  • /engineering and technology/industrial biotechnology/biomaterials
  • /medical and health sciences/basic medicine/neurology/parkinson
  • /humanities/languages and literature/linguistics/phonetics

Call for proposal

H2020-PHC-2014-two-stage
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

AZIENDA UNITA' SANITARIA LOCALE DI BOLOGNA
Address
Via Castiglione 29
40124 Bologna
Italy
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
EU contribution
€ 745 437,50

Participants (8)

UNIVERSITY COLLEGE LONDON
United Kingdom
EU contribution
€ 997 057,50
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS
Germany
EU contribution
€ 720 968,75
Address
Robert-koch-strasse 40
37075 Goettingen
Activity type
Higher or Secondary Education Establishments
SERVICIO ANDALUZ DE SALUD
Spain
EU contribution
€ 671 167,50
Address
Avenida De La Constitucion 18
41071 Sevilla
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
PERSONAL GENOMICS SRL
Italy
EU contribution
€ 635 875
Address
Via Roveggia 43
37136 Verona
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 308 123,75
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
CONSORZIO INTERUNIVERSITARIO RISONANZE MAGNETICHE DI METALLO PROTEINE
Italy
EU contribution
€ 721 261,25
Address
Piazza San Marco 4
50121 Firenze
Activity type
Higher or Secondary Education Establishments
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 901 232,50
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments
ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Italy
EU contribution
€ 292 252,25
Address
Via Zamboni 33
40126 Bologna
Activity type
Higher or Secondary Education Establishments