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P75NTR

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Understanding death receptor signaling and physiology in the nervous system A r...

Understanding death receptor signaling and physiology in the nervous system A roadmap for the development of new treatments to neurodegenerative diseases and neurotrauma The aim of this proposal is to elucidate the molecular mechanisms and physiological relevance of death-receptor signaling in the nervous system and to harness this knowledge for the development of novel treatments to neurodegenera... ver más

31/05/2020

3M€

Presupuesto del proyecto: 3M€

Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2020-05-31 No tenemos la información de la convocatoria

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Información adicional privada

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

1 Participantes

0.00€ | Lider

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Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 3M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The aim of this proposal is to elucidate the molecular mechanisms and physiological relevance of death-receptor signaling in the nervous system and to harness this knowledge for the development of novel treatments to neurodegenerative diseases and neurotrauma. The main focus is on the p75 neurotrophin receptor (p75NTR), which is predominantly expressed in the developing nervous system and is highly induced upon different types of adult neural injury. Additional studies on other death receptors, such as DR6, are also described. p75NTR signaling can induce neuronal death, reduce axonal growth and decrease synaptic function, hence there is a good rationale for inhibiting p75NTR in neural injury and neurodegeneration. Recent discoveries from my laboratory have clarified the mechanism of p75NTR activation and provided new insights into the underlying logic of p75NTR signaling, paving the way for a genetic dissection of p75NTR function and physiology. These discoveries have open new avenues to elucidate the molecular mechanisms underlying ligand-specific responses and downstream signal propagation by death-receptors, unravel the physiological relevance of death-receptor signaling pathways in health and disease, and develop new strategies to block death-receptor activity in neural injury and neurodegeneration. To drive progress in this research area it is proposed to: i) Elucidate the mechanisms by which p75NTR and other death receptors become activated by different ligands and elicit distinct, ligand-specific cellular responses; ii) Elucidate the mechanisms underlying the specificity and diversity of p75NTR signaling and decipher their underlying logic; iii) Elucidate the physiological significance of distinct p75NTR signaling pathways through genetic dissection in knock-in mice; iv) Harness this knowledge to identify and characterize novel p75NTR inhibitors. This is research of a high-gain/high-risk nature, posed to open unique opportunities in research & development.

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