Objective
The life essential element iron is required as a cofactor in central nervous system metabolic processes, but unbound iron catalyzes the production of toxic reactive oxygen species. Neuronal iron accumulation is a common pathological feature in the cortex in Alzheimer’s disease (AD), the substantia nigra (SN) in Parkinson’s disease (PD), and the tauopathies. Since too much or too little iron can compromise cell viability, cellular iron homeostasis is tightly regulated. Ferroxidases, oxidize Fe2+ to Fe3+, and are essential for maintaining intracellular iron homeostasis. A deficiency in the surface presented ferroxidase leads to toxic iron accumulation and degeneration. Ferroxidase activities in the brain may fail with aging and a range of neurodegenerative disorders (ND), possibly contributing to disease pathogenesis.
My group has discovered that the ferroxidase activity of β-amyloid precursor protein (APP) is essential for neuronal iron efflux and inhibited APP ferroxidase activity parallels iron accumulation in some ND. Disruption in the correct localization of a ferroxidase may be fundamental in the disease process. Of relevance, neuronal anterograde transport of APP requires tau and we have recently shown decreased tau expression impairs the presence of cell surface APP leading to inefficient efflux of iron and intensifying the risk of excitotoxicty within the region via intraneuronal iron accumulation.
Primary aims will elucidate the role of APP trafficking and processing on iron efflux regulation within general neurobiology and investigate this mechanism in iron accumulating age- and pathologically- affected neurons already known to have problems with APP, tau and excitotoxicity.
Some current therapeutic compounds for ND are proposed to work via restoring metal homeostasis. A final aim will determine if these compounds, as well as a number of novel derivatives, work through a pathway that restores APP to its correct function in neuronal iron efflux.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology parkinson
- medical and health sciences basic medicine physiology homeostasis
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-CIG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
LS2 9JT Leeds
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.