Project description
Antisense oligonucleotides as a novel intervention against neurodegeneration
The tau protein plays a key role in neurotransmission by binding to the cytoskeleton of neurons and assisting the trafficking of neurotransmitter vesicles to the synapse. The accumulation of pathogenic forms of tau reduces vesicle mobility and neurotransmitter release, impairing neural communication and leading to various neurodegenerative conditions including Alzheimer's disease. The EU-funded TARGET_SYNAPTIC_TAU project is focusing on the interaction of tau with the synaptic vesicle-associated protein Synaptogyrin-3. The rationale is to employ antisense oligonucleotides to reduce the levels of Synaptogyrin-3 and thus block the binding of pathogenic tau to synaptic vesicles. Scientists will test this approach as an intervention against tauopathies.
Objective
Tauopathies (that include Alzheimer’s disease) are characterized by hyperphosphorylation or mutations in the microtubuleassociated protein Tau. This reduces the affinity of Tau to bind microtubules and increases the levels of soluble detached Tau in neurons. Previous ERC-supported work from my lab showed that pathogenic Tau accumulates at pre-synaptic terminals and clusters synaptic vesicles in mouse and fly Tauopathy models and in Alzheimer patient brain samples. This pre-synaptic Tau reduces vesicle mobility and neurotransmitter release (Zhou et al., 2017). The interaction of Tau with synaptic vesicles occurs via the synaptic vesicle-associated protein Synaptogyrin-3. Lowering the levels of Synaptogyrin-3 blocks the ability of Tau to efficiently bind to synaptic vesicles (McInnes et al., 2018). Hence, Synaptogyrin-3 is a promising therapeutic target to tackle tauopathies. In this project I propose to use antisense oligonucleotides (ASOs) to reduce the levels of Synaptogyrin-3 in the brain of Tauopathy mouse models to rescue tau-induced pre-synaptic defects, including cognitive decline. ASO-technology has vastly improved over the past years and was recently approved to treat other degenerative disorders. My goal is to provide in vivo proof-of-concept that targeting Synaptogyrin-3 with an ASO in a therapeutic setting suppresses Tau-induced defects, including cognitive decline.
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 genetics mutation
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Topic(s)
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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.
ERC-POC - Proof of Concept Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2020-PoC
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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.
9052 ZWIJNAARDE - GENT
Belgium
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