NEURONAL SPECIFICITY
Longitudinal analysis to study neurodegenerative diseases mechanisms in specific neuronal subtypes
| Coordinatore | FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Organization address
address: AVENIDA DE PIO XII 55 contact info |
| Nazionalità Coordinatore | Spain [ES] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2007-4-3-IRG |
| Funding Scheme | MC-IRG |
| Anno di inizio | 2009 |
| Periodo (anno-mese-giorno) | 2009-05-01 - 2013-04-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Organization address
address: AVENIDA DE PIO XII 55 contact info |
ES (PAMPLONA) | coordinator | 0.00 |
Mappa
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Obiettivo del progetto (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.'