Summary
The aim of this action is to understand the mechanisms behind the susceptibility of enthorinal cortex II (ECII) neurons to neurofibrillary tangle (NFT) formation in Alzheimer´s disease. To do so we will modulate the expression of the genes that according to NetWAS (Network-wide Association Study) are more directly involved in NFT formation in ECII neurons.
Understanding why the pathological lesions that lead to neurodegeneration appear earlier in some specific neurons of the human brain is one of the major challenges in the neuroscience field.
Prof. Greengard´s lab has generated a transgenic mouse that allows the immunoprecipitation of ribosome-bound mRNAs specifically from ECII neurons (ECII-bacTRAP mice). We will perform AAV stereotaxic injections in the enthorinal cortex of these mice followed by RNA-seq to determine how the modulation of our target genes affects ECII neurons expression profile. We will also explore whether our intervention can influence ECII neurons susceptibility to NFT in P301S AD mice. The results obtained in mice will be validated by immunofluorescence and in situ hybridization studies in human samples from control and AD patients at different Braak stages.
Our results could add extremely relevant information on the mechanisms underlying AD pathogenesis and reveal these genes as new therapeutic targets for the disease.
Understanding why the pathological lesions that lead to neurodegeneration appear earlier in some specific neurons of the human brain is one of the major challenges in the neuroscience field.
Prof. Greengard´s lab has generated a transgenic mouse that allows the immunoprecipitation of ribosome-bound mRNAs specifically from ECII neurons (ECII-bacTRAP mice). We will perform AAV stereotaxic injections in the enthorinal cortex of these mice followed by RNA-seq to determine how the modulation of our target genes affects ECII neurons expression profile. We will also explore whether our intervention can influence ECII neurons susceptibility to NFT in P301S AD mice. The results obtained in mice will be validated by immunofluorescence and in situ hybridization studies in human samples from control and AD patients at different Braak stages.
Our results could add extremely relevant information on the mechanisms underlying AD pathogenesis and reveal these genes as new therapeutic targets for the disease.
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| Web resources: | https://cordis.europa.eu/project/id/799638 |
| Start date: | 01-09-2018 |
| End date: | 01-10-2021 |
| Total budget - Public funding: | 247 059,00 Euro - 247 059,00 Euro |
Cordis data
Original description
The aim of this action is to understand the mechanisms behind the susceptibility of enthorinal cortex II (ECII) neurons to neurofibrillary tangle (NFT) formation in Alzheimer´s disease. To do so we will modulate the expression of the genes that according to NetWAS (Network-wide Association Study) are more directly involved in NFT formation in ECII neurons.Understanding why the pathological lesions that lead to neurodegeneration appear earlier in some specific neurons of the human brain is one of the major challenges in the neuroscience field.
Prof. Greengard´s lab has generated a transgenic mouse that allows the immunoprecipitation of ribosome-bound mRNAs specifically from ECII neurons (ECII-bacTRAP mice). We will perform AAV stereotaxic injections in the enthorinal cortex of these mice followed by RNA-seq to determine how the modulation of our target genes affects ECII neurons expression profile. We will also explore whether our intervention can influence ECII neurons susceptibility to NFT in P301S AD mice. The results obtained in mice will be validated by immunofluorescence and in situ hybridization studies in human samples from control and AD patients at different Braak stages.
Our results could add extremely relevant information on the mechanisms underlying AD pathogenesis and reveal these genes as new therapeutic targets for the disease.
Status
CLOSEDCall topic
MSCA-IF-2017Update Date
28-04-2024
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