Objective
Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) are the most common human neurodegenerative diseases. Each features an abnormal accumulation of proteins, but whether the aggregation leads to neuronal death is controversial. HD is caused by a single mutation that increases the number of CAG repeats. Mutant huntingtin (htt) forms intraneuronal inclusion bodies (IBs). To determine if IBs are pathogenic, incidental, or a beneficial coping response, we developed an automated microscope system that enabled us to follow individual neurons over long periods of time. We prospectively measured the survival time of individual neurons and simultaneously monitored features, such as htt expression levels and IB formation. Using survival analysis methods, we sought to identify the best predictor of neuronal death. We found that the amount of diffuse mutant htt predicted death and that IB formation decreased the risk of neuronal death. Thus, IB formation may be a coping response against the more toxic diffuse mutant htt forms. Another common pathological hallmark of neurodegenerative disorders is a strong specificity for the affected neuronal populations. Paradoxically, the proteins affected in these diseases are ubiquitously expressed and yet only specific subsets of neurons are affected. Interestingly, areas less affected in HD brain patients show more IBs. Because aggregation and neuronal specificity are hallmarks of neurodegenerative diseases, we hypothesize that the different capacities of neuronal subtypes for handling mutant proteins (i.e. efficient aggregation or/and activating degradation pathways) explain differences in survival among neuronal types. We will express proteins affected in htt variants or PD (mutant versions of LRRK2) in different subtypes of primary neurons. Using longitudinal survival, we will determine if aggregation or degradation determines survival or death differentially in particular neuronal subtypes.
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 biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine neurology parkinson
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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.
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-2007-4-3-IRG
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
31008 Pamplona
Spain
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.