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Do nanoparticles induce neurodegenerative diseases? Understanding the origin of reactive oxidative species and protein aggregation and mis-folding phenomena in the presence of nanoparticles

Objective

As the use of nanoparticles becomes more prevalent, it is clear that human exposure will inevitably increase. Considering the rapidly ageing European population and the resulting increase in the incidence of neurodegenerative diseases, there is an urgent need to address the risk presented by nanoparticles towards neurodegenerative diseases. It is believed that nanoparticles can pass through the blood-brain barrier. Once in the brain, nanoparticles have two potential major effects. They can induce oxidative activity (production of Reactive Oxygen Species), and can induce anomalous protein aggregation behaviour (fibrillation). There are multiple disease targets for the nanoparticles, including all of the known fibrillation diseases (e.g. Alzheimer’s and Parkinson’s diseases). The factors that determine which nanoparticles enter the brain are not known. Nanoparticle size, shape, rigidity and composition are considered important, and under physiological conditions, the nature of the adsorbed biomolecule corona (proteins, lipids etc.) determines the biological responses. The NeuroNano project will investigate the detailed mechanisms of nanoparticle passage through the blood-brain barrier using primary cell co-cultures and animal studies. Using nanoparticles that are shown to reach the brain, we will determine the mechanisms of ROS production and protein fibrillation, using state-of-the-art approaches such as redox proteomics and isolation/characterisation of the critical pre-fibrillar species. Animal models for Alzheimer’s diseases will confirm the effects of the nanoparticles in vivo. At all stages the exact nature of the nanoparticle biomolecule corona will be determined. The result will be a risk-assessment framework for assessing the safety of nanoparticles towards neurodegenerative diseases, based on the connection of their biological effects to their biomolecule corona, which determines the biological response in vivo and reports on the nanoparticles’ history.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/lipids
  • /medical and health sciences/basic medicine/neurology/parkinson
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /humanities/history and archaeology/history
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics
  • /medical and health sciences/basic medicine/neurology/alzheimer

Call for proposal

FP7-NMP-2007-SMALL-1
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Address
Belfield
4 Dublin
Ireland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 884 061,75
Administrative Contact
Donal Doolan (Mr.)

Participants (10)

THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 251 621,25
Address
Old College, South Bridge
EH8 9YL Edinburgh
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Angela Noble (Ms.)
UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Ireland
EU contribution
€ 167 000
Address
Western Road
T12 YN60 Cork
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Pater Kennedy (Prof.)
UNIVERSITY OF ULSTER
United Kingdom
EU contribution
€ 420 617
Address
Cromore Road
BT52 1SA Coleraine
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Anne Marie Patton (Dr.)
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany
EU contribution
€ 337 500
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Activity type
Research Organisations
Administrative Contact
Juergen Ertel (Dr.)
JRC -JOINT RESEARCH CENTRE- EUROPEAN COMMISSION
Belgium
EU contribution
€ 352 200
Address
Rue De La Loi 200
1049 Brussels
Activity type
Research Organisations
Administrative Contact
Raymond Crandon (Mr.)
UNIVERSITY OF ROCHESTER
United States
Address
Elmwood Avenue, Box Ehsc 601
14642 Rochester Ny
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jane Tolbert (Dr.)
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
United States
Address
Franklin Street 1111, 12 Floor
94607 Oakland Ca
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Evelyn Balabis (Ms.)
WILLIAM MARSH RICE UNIVERSITY
United States
Address
Main Street 6100
77005 Houston Texas
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nancy Nisbett (Ms.)
NATIONAL INSTITUTE FOR MATERIALS SCIENCE
Japan
Address
Sengen 1-2-1
305 0047 Tsukuba
Activity type
Research Organisations
Administrative Contact
Masahiro Takemura (Mr.)
UNIVERSIDADE FEDERAL DO CEARA
Brazil
EU contribution
€ 85 000
Address
Avenida Da Universidade 2853
60020181 Fortaleza
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Francisco Antonio Guimaraes (Dr.)