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NeuroFish

Financiado

Cerrado

Neurofilaments in Health and neurodegenerative diseases

Neurofilaments (NFs) are a highly dynamic cytoskeletal network, which exhibits essential functions in neurons and are key actors in neurodegeneration. NFs are not only a genetic cause of neuronal death in human, their abnormal agg... ver más

31/12/2027

INSERM

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-04-06

ERC-2019-COG: ERC Consolidator Grant

I+D

Cerrada hace 5 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

INSERM

1.87M€ | Lider

AGRICULTURA Y CONSERVAS

1.54M€ | Participante

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Duración del proyecto: 92 meses Fecha Inicio: 2020-04-06
Fecha Fin: 2027-12-31

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Neurofilaments (NFs) are a highly dynamic cytoskeletal network, which exhibits essential functions in neurons and are key actors in neurodegeneration. NFs are not only a genetic cause of neuronal death in human, their abnormal aggregation is an early pathological hallmark in disease, and their genetic removal from axons has shown spectacular benefits in delaying disease onset, extending survival and restoring neurological functions in mouse models. In this project, I propose the concept that the defects in NF transport and degradation are the causes of neurodegeneration. I will tackle the live dynamic of these processes in health and disease in a meaningful in vivo context, using the zebrafish. Combining state-of-the-art and innovative live-imaging and proteomic methodologies in zebrafish, our program has three major goals. First, we will study the dynamic of NF transport along the axons and its spatial regulation by myelinating cells, with novel zebrafish lines expressing fluorescently labeled NFs. Second, we will decipher the mechanisms of NF degradation by generating a zebrafish line overexpressing gigaxonin, an E3 ligase adaptor we found to destroy the stable NF network, and by designing a new proteomic methodology in zebrafish. Finally, we will investigate NF dysfunctions and their pathological roles in disease, by generating models for neurodegenerative diseases carrying NF mutations and using the methodologies described above. I anticipate that interventions on NF dynamics will substantially reverse neurodegeneration, and proofs of concept will be obtained by overexpressing gigaxonin in our disease zebrafish models and through drug screening. Thus, this ERC project will generate forefront knowledge in the field of NFs and neurodegeneration and will provide a highly significant platform for therapeutic intervention on NFs, for the benefit of most neurodegenerative diseases.

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