EXOSOMES_AD | The role of extracellular vesicles in Alzheimer’s Disease: towards obtaining mechanistic insights to intrinsic protection mechanisms

Summary
Alzheimer’s disease (AD) is the leading cause of dementia worldwide (>30 million people). The cause of the disease is not known, and there is no causal treatment. Extracellular vesicles (EVs), including exosomes and microvesicles, are structures released by most if not all cells. EVs carry competent signalling proteins, lipids and nucleic acids, participating in cell-to-cell communication. Recently, EVs emerged as relevant actors in neurodegenerative diseases, especially in AD, and they were described as biomarkers in patient’s fluids. Interestingly, they seem to have a dual role in AD: spreading of pathological aggregates, and neuroprotection against the progression of the pathology. In this project, I will describe in detail the EVs biology in AD elucidating how they act neuroprotective. I will characterise the composition, source and uptake mechanisms of EVs throughout AD progression. I will extract EVs from brains of AD patients (sporadic and familial) and age/sex-matched controls in two stages of the disease. RNA and protein profile will be characterised by novel RNA sequencing and mass spectrometry technics. From these omics analysis, protein and gene candidates related to the EVs functions in AD will emerge. Moreover, to investigate putative mechanisms of neuroprotection in AD, I will treat neural cultures from hiPSCs with AD-derived EVs and stress them with AD-like inputs. The effects of these treatments will be assessed by advanced analysis (i.e. Ca2+ imaging, and mitochondrial trafficking analysis). The endocytic pathways and surface proteins involved in EVs’ uptake will also be evaluated. Finally, AD-iPSC cultures will be used to functionally modify the targets obtained from the omics analysis to foster their neuroprotective role in AD.
My project will generate mechanistic insight in EVs’ neuroprotection in AD by combing the deep phenotyping of patient-derived EVs with hypothesis-driven experiments in hiPSC to open the door to new EV-based AD treatment.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101030402
Start date: 15-04-2021
End date: 14-04-2024
Total budget - Public funding: 244 209,60 Euro - 244 209,00 Euro
Cordis data

Original description

Alzheimer’s disease (AD) is the leading cause of dementia worldwide (>30 million people). The cause of the disease is not known, and there is no causal treatment. Extracellular vesicles (EVs), including exosomes and microvesicles, are structures released by most if not all cells. EVs carry competent signalling proteins, lipids and nucleic acids, participating in cell-to-cell communication. Recently, EVs emerged as relevant actors in neurodegenerative diseases, especially in AD, and they were described as biomarkers in patient’s fluids. Interestingly, they seem to have a dual role in AD: spreading of pathological aggregates, and neuroprotection against the progression of the pathology. In this project, I will describe in detail the EVs biology in AD elucidating how they act neuroprotective. I will characterise the composition, source and uptake mechanisms of EVs throughout AD progression. I will extract EVs from brains of AD patients (sporadic and familial) and age/sex-matched controls in two stages of the disease. RNA and protein profile will be characterised by novel RNA sequencing and mass spectrometry technics. From these omics analysis, protein and gene candidates related to the EVs functions in AD will emerge. Moreover, to investigate putative mechanisms of neuroprotection in AD, I will treat neural cultures from hiPSCs with AD-derived EVs and stress them with AD-like inputs. The effects of these treatments will be assessed by advanced analysis (i.e. Ca2+ imaging, and mitochondrial trafficking analysis). The endocytic pathways and surface proteins involved in EVs’ uptake will also be evaluated. Finally, AD-iPSC cultures will be used to functionally modify the targets obtained from the omics analysis to foster their neuroprotective role in AD.
My project will generate mechanistic insight in EVs’ neuroprotection in AD by combing the deep phenotyping of patient-derived EVs with hypothesis-driven experiments in hiPSC to open the door to new EV-based AD treatment.

Status

SIGNED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2020
MSCA-IF-2020 Individual Fellowships