Objective
Inhibitory chondroitin sulphate proteoglycans (CSPGs) have several roles in CNS damage and repair, revealed by their digestion with chondroitinase. Most recently, digestion of CSPGs in the limbic system and cortex has led to a very substantial enhancement of memory.
The effects of CSPGs on plasticity and memory are largely through their concentration into PNNs, because transgenics lacking the PNN component link protein in the CNS have very attenuated PNNs, and show continuing plasticity into adulthood, and enhanced memory in just the same way as chondroitinase-treated animals. The PNN is therefore a novel therapeutic target that has not been explored.
This application focuses particularly on enhancement of memory through manipulation of PNNs.
In Alzheimer’s disease (AD) and ageing the main cognitive disability is loss of memory. The enhancement of memory following chondroitinase treatment or PNN knockout in object memory is many times greater than obtained using cholinesterase inhibitors (the only currently available treatment for memory enhancement). PNN manipulation is therefore a particularly promising avenue for developing treatments to overcome the main cognitive disability of AD and ageing.
The aims of the application are:
1. Test the extent of memory enhancement due to PNN manipulation in models of AD due to Abeta, tau mutations and in aged CNS.
2. Establish the molecular mechanism for PNN effects on memory, focusing on Semaphorin3 presentation by PNNs, and direct effects via the PTPsigma receptor.
3. Discover the sulphation modifications of the CSPG glycan chains that enable binding of Semaphorin3s, activation of the PTPsigma receptor.
4. Analyse molecules that bind to PNN glycans, to identify new potential effectors of PNN effects on memory and plasticity
5. Testing in memory and plasticity models of novel PNN-targeted approaches.
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
- natural sciences biological sciences biochemistry biomolecules carbohydrates
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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.
ERC-2011-ADG_20110310
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.
Host institution
CB2 1TN CAMBRIDGE
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.