Project description
Extracellular vesicles in Alzheimer’s disease: pathogenesis or neuroprotection?
Most cells secrete extracellular vesicles (EVs) that contain various biomolecules including RNA and proteins. Emerging evidence indicates that EVs may have a dual role in Alzheimer’s disease (AD) contributing to both disease pathogenesis through spreading of protein aggregates and neuroprotection. The EU-funded EXOSOMES_AD project will characterise the composition of EVs from AD patients and identify protein and gene candidates related to neuroprotection. Insight into the mechanisms of neuroprotection in AD may lead to novel interventions that can delay or even prevent disease onset. Given that AD is the most prevalent age-related neurodegenerative condition, such a prospect will improve the quality of life of millions of people worldwide.
Objective
Alzheimer’s disease (AD) is the leading cause of dementia worldwide (>30 million people). The cause of the disease is not known, and there is no causal treatment. Extracellular vesicles (EVs), including exosomes and microvesicles, are structures released by most if not all cells. EVs carry competent signalling proteins, lipids and nucleic acids, participating in cell-to-cell communication. Recently, EVs emerged as relevant actors in neurodegenerative diseases, especially in AD, and they were described as biomarkers in patient’s fluids. Interestingly, they seem to have a dual role in AD: spreading of pathological aggregates, and neuroprotection against the progression of the pathology. In this project, I will describe in detail the EVs biology in AD elucidating how they act neuroprotective. I will characterise the composition, source and uptake mechanisms of EVs throughout AD progression. I will extract EVs from brains of AD patients (sporadic and familial) and age/sex-matched controls in two stages of the disease. RNA and protein profile will be characterised by novel RNA sequencing and mass spectrometry technics. From these omics analysis, protein and gene candidates related to the EVs functions in AD will emerge. Moreover, to investigate putative mechanisms of neuroprotection in AD, I will treat neural cultures from hiPSCs with AD-derived EVs and stress them with AD-like inputs. The effects of these treatments will be assessed by advanced analysis (i.e. Ca2+ imaging, and mitochondrial trafficking analysis). The endocytic pathways and surface proteins involved in EVs’ uptake will also be evaluated. Finally, AD-iPSC cultures will be used to functionally modify the targets obtained from the omics analysis to foster their neuroprotective role in AD.
My project will generate mechanistic insight in EVs’ neuroprotection in AD by combing the deep phenotyping of patient-derived EVs with hypothesis-driven experiments in hiPSC to open the door to new EV-based AD treatment.
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.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine pathology
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
20251 Hamburg
Germany
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.