Summary
Parkinsonian disorders (PDs) affect more than 1.2 million people in Europe with an estimated cost of €13.9 billion annually and have no cure. PDs have long been characterized by decreased motor activity, which is caused by the loss of dopaminergic neurons. Several disturbed processes have been described such as proteostasis, mitochondrial function and neuroinflammation, but its molecular mechanisms and their interactions are essentially unknown. There are recent evidences of alterations in the interferons’ (IFN) signalling involved in the neuroinflammatory processes of PDs. The host lab discovered the essential role of IFNβ signalling in the neuronal homeostasis of PD. The IFNβ receptor (IFNAR) plays a key role in the control of IFNβ cellular responses. However, the regulatory mechanisms, at level of its membrane subunits IFNAR 1 and 2, and especially its soluble receptor sIFNAR2 have not been characterized in PD-associated neuroinflammatory context. Most remarkably, the host lab has also identified a new mutation in IFNAR1 associated with a family of PD patients, and I have found that PDs present lower serum levels of sIFNAR2 than controls indicating dysregulation in this pathway. Based on our findings, I hypnotise that a defective IFNβ-IFNAR signalling is associated with PD pathology and this could be partly mediated by the function of sIFNAR2 as this protein is able to modulate the endogenous IFNβ and interplay with membrane-expressed IFNAR1 or IFNAR2. Fulfilling the tasks of this proposal will have strong potential to reveal the mode of action of sIFNAR2, as IFNβ-IFNAR signalling regulator, and as a novel molecule with intrinsic activities in maintaining & restoring the neuronal homeostasis and therefore could identify novel targets for treatment of PD. Through this MSCA-IF I would benefit from a unique training and expertise in one of the most cutting-edge laboratories of the research proposed here, and it will impact extremely my future scientific career.
Unfold all
/
Fold all
More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/893859 |
| Start date: | 14-09-2020 |
| End date: | 13-09-2022 |
| Total budget - Public funding: | 207 312,00 Euro - 207 312,00 Euro |
Cordis data
Original description
Parkinsonian disorders (PDs) affect more than 1.2 million people in Europe with an estimated cost of €13.9 billion annually and have no cure. PDs have long been characterized by decreased motor activity, which is caused by the loss of dopaminergic neurons. Several disturbed processes have been described such as proteostasis, mitochondrial function and neuroinflammation, but its molecular mechanisms and their interactions are essentially unknown. There are recent evidences of alterations in the interferons’ (IFN) signalling involved in the neuroinflammatory processes of PDs. The host lab discovered the essential role of IFNβ signalling in the neuronal homeostasis of PD. The IFNβ receptor (IFNAR) plays a key role in the control of IFNβ cellular responses. However, the regulatory mechanisms, at level of its membrane subunits IFNAR 1 and 2, and especially its soluble receptor sIFNAR2 have not been characterized in PD-associated neuroinflammatory context. Most remarkably, the host lab has also identified a new mutation in IFNAR1 associated with a family of PD patients, and I have found that PDs present lower serum levels of sIFNAR2 than controls indicating dysregulation in this pathway. Based on our findings, I hypnotise that a defective IFNβ-IFNAR signalling is associated with PD pathology and this could be partly mediated by the function of sIFNAR2 as this protein is able to modulate the endogenous IFNβ and interplay with membrane-expressed IFNAR1 or IFNAR2. Fulfilling the tasks of this proposal will have strong potential to reveal the mode of action of sIFNAR2, as IFNβ-IFNAR signalling regulator, and as a novel molecule with intrinsic activities in maintaining & restoring the neuronal homeostasis and therefore could identify novel targets for treatment of PD. Through this MSCA-IF I would benefit from a unique training and expertise in one of the most cutting-edge laboratories of the research proposed here, and it will impact extremely my future scientific career.Status
CLOSEDCall topic
MSCA-IF-2019Update Date
28-04-2024
Images
No images available.
Geographical location(s)
