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InflaPML SIGNED

Promyelocytic leukemia protein (PML) outside the tumor: a new player in the control of inflammation

Total Cost €

0

EC-Contrib. €

0

Partnership

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 InflaPML project word cloud

Explore the words cloud of the InflaPML project. It provides you a very rough idea of what is the project "InflaPML" about.

components    link    brain    players    beta    compartments    regulated    de    mitochondria    penetrant    tumour    damaged    treat    neurodegenerative    acting    follow    goals    endoplasmic    shown    clinically    immune    therapy    modulation    anti    pharmacological    site    modulator    cellular    inflammasome    stroke    arise    interfaces    inflammatory    assembly    unexpected    nervous    mechanism    transcriptionally    neurological    pathologic    pathologies    p2x7    of    pml    overcome    il    therapies    nlrp3    disease    bases    neuronal    underlying    epilepsy    hypothesize    neuroinflammatory    consistently    elusive    sterile    inflammation    axis       worsening    release    linked    antagonists    survival    prognostic    environment    neuroinflammation    neurodegeneration    sustains    recruiting    unsuccessful    persistent    unfortunately    drugs    regulation    local    diseases    function    controls    post    outside    influence    prognosis    prove    mams    illnesses    reticulum    progression    molecular    existence    er   

Project "InflaPML" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI FERRARA 

Organization address
address: VIA ARIOSTO 35
city: FERRARA
postcode: 44121
website: www.unife.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 1˙462˙500 €
 EC max contribution 1˙462˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-03-01   to  2025-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI FERRARA IT (FERRARA) coordinator 1˙462˙500.00

Map

 Project objective

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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The information about "INFLAPML" are provided by the European Opendata Portal: CORDIS opendata.

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