InflaPML
Financiado
Promyelocytic leukemia protein PML outside the tumor a new player in the cont...
Promyelocytic leukemia protein PML outside the tumor a new player in the control of inflammation
Local sterile inflammation arise in many pathologic states, including several diseases of the nervous system as brain stroke, neurodegenerative diseases and epilepsy. The persistent and de-regulated inflammatory response sustains...
Local sterile inflammation arise in many pathologic states, including several diseases of the nervous system as brain stroke, neurodegenerative diseases and epilepsy. The persistent and de-regulated inflammatory response sustains these neurological pathologies worsening their prognosis. Different molecular players, as NLRP3 and P2X7 have been shown to contribute to the progression of these illnesses triggering the release of IL-1β and recruiting cellular components of the immune response at the neurodegeneration site. Consistently, brain penetrant P2X7 antagonists are clinically used to treat epilepsy and neurodegenerative diseases, while the pharmacological modulation of IL-1β is still unsuccessful. Unfortunately, the molecular mechanism underlying neuroinflammation and NLRP3 inflammasome assembly remains elusive. Here we propose that different neuroinflammatory diseases can be linked together in a common disease pathway, of which damaged function should be targeted for therapy. Specifically we propose a new mechanism acting on IL-1β regulation: we hypothesize the existence of a new activity of PML outside tumour environment, acting at the endoplasmic reticulum-mitochondria interfaces (MAMs) as modulator of NLRP3 inflammasome. On these bases, I propose a project in which PML activity at MAMs can be the key link of different neuroinflammatory diseases. Our goals are as follow: 1) to demonstrate that PML post-transcriptionally controls NLRP3 activity at the ER/MAMs compartments and thus IL-1β release via P2X7; 2) to prove that IL-1β release have a strong influence on neuronal environment and survival, and might represent a prognostic factor; 3) to develop new drugs targeting PML/NLRP3/P2X7 axis to overcome the unexpected failure of anti-IL-1 therapies.
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Duración del proyecto: 66 meses
Fecha Inicio: 2019-11-29
Fecha Fin: 2025-05-31
Fecha Fin: 2025-05-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-11-29
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG:
ERC Starting Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
UNIVERSITA DEGLI STUDI DI FERRARA
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
272.62K€ |
Participante