Objective
Neuroinflammation plays a crucial role in the development and progression of neurodegenerative diseases such as Alzheimer’s or ischemic stroke. The inflammatory response is coordinated by resident cells (microglia) that upon activation produce pro-inflammatory mediators including cytokines, chemokines and reactive oxygen species. Identification of small molecules that alleviate microglia inflammation is therefore pivotal in uncovering feasible therapeutic approaches to treat brain disorders. Emerging evidence indicates that carbon monoxide (CO), which is endogenously produced in cells by the enzyme heme oxygenase-1 (HO-1), functions as an important signaling mediator endowed with strong anti-inflammatory activities. However, the mode(s) by which CO elicits these effects remains to be elucidated. Although CO is a renowned inhibitor of mitochondrial respiration at high concentrations, recent results reveal that low doses of CO positively modulate mitochondrial function. The current proposal aims to investigate how the interaction of CO with mitochondria affects its anti-inflammatory activity in microglia. Innovative chemical entities and methodological approaches will be employed to dissect the different functions of CO in this context, including: 1) CO-releasing molecules, which deliver precise amounts of CO to biological systems; 2) a new class of hybrid molecules composed of a CO-releasing moiety coordinated to an electrophilic structure known to induce HO-1 expression; 3) a Seahorse Analyser to perform an in-depth biochemical analysis of the effect(s) of CO on mitochondrial bioenergetics and how this may lead to a reduced inflammatory response, and; 4) whole-genome transcriptome profiling of primary microglia cells focusing on the effects of CO on genes involved in cell metabolism and inflammation. This project will provide the first comprehensive investigation into the networks that are involved in the anti-inflammatory activity of this ephemeral signaling gas.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences chemical sciences inorganic chemistry inorganic compounds
- natural sciences biological sciences cell biology cell metabolism
- medical and health sciences basic medicine neurology stroke
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2013-IEF
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.
Coordinator
75654 PARIS
France
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.