REMIND
Financiado
Targeting pathological synaptic pruning by microglia in neurodegeneration
Synapse loss is the major correlate of cognitive impairment in many neurodegenerative diseases. Recent literature suggests that microglia, which mediate synaptic pruning during brain development, can be responsible for synapse los...
Synapse loss is the major correlate of cognitive impairment in many neurodegenerative diseases. Recent literature suggests that microglia, which mediate synaptic pruning during brain development, can be responsible for synapse loss in neurodegeneration. Although the underlying mechanisms are poorly understood, growing evidence indicates that dysfunctional microglia affect synapses number and function in pathology. Genome-wide association studies reveal that the majority of risk genes associated with neurodegenerative disorders are highly expressed in microglia. While such studies clearly implicate these cells in the pathogenesis of the disease, little is known about the causal mechanisms that link microglial risk variants to loss of synapses.
We will identify the molecular mechanisms involved in microglia-mediated synapse loss. We will also generate novel in vitro and ex vivo models of ‘risk microglia’, by introducing genetic variants associated with cognitive impairment –alone or in combination- specifically in microglia, taking advantage of CRISPR/ Cas9 genome editing techniques. These goals will be achieved by combining cutting-edge transcriptomics and proteomics with mouse models of intense synaptic remodelling, to reveal the unique molecular signature of ‘shaper microglia’. A multidisciplinary approach will allow the extensive characterisation of risk models, by combining metabolic analysis, synaptic phagocytosis and degradation assays, with super-resolution microscopy, and novel genetically encoded labelling methods. With the knowledge generated here, we aim at developing and validating in vivo novel drugs- and nanobodies-based approaches for effective targeting of pathological pruning.
In summary, REMIND will focus on:
1) Identifying molecular players in microglial-mediated synapse loss
2) Generating ‘risk microglia’ models, to asses the role of genetic variants associated with neurodegeneration
3) Developing novel strategies for targeting prunining
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Duración del proyecto: 74 meses
Fecha Inicio: 2018-10-30
Fecha Fin: 2024-12-31
Fecha Fin: 2024-12-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2018-10-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2018-STG:
ERC Starting Grant
Cerrada
hace 7 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
swiss aeropole SA
No se ha especificado una descripción o un objeto social para esta compañía.
346.26K€ |
Participante