H2020Индивидуална стипендия2020–2022

ParkIFNAR · Soluble IFNAR2 in Parkinson's disease and its role in the regulation of IFNβ in a neuroinflammatory context.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-09-14 → 2022-09-13
Финансиране от ЕС: 207 312 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ролята на разтворимия рецептор sIFNAR2 и неговото влияние върху сигналите на интерферон бета се изследва при болест на Паркинсон. Това помага за разбирането на невровъзпалението и начина, по който дефектите в тези процеси допринасят за развитието на заболяването.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Soluble IFNAR2 in Parkinson's disease and its role in the regulation of IFNβ in a neuroinflammatory context.

Over 1.2 million people in Europe alone suffer from Parkinsonian disorders (PD), and it has a rising prevalence. This neurodegenerative condition led to decreased motor activity and other complications including cognitive impairment. Current medications for patients are focused on treating the symptoms, however, no curative treatment is available. Evidence indicates that neuroinflammation is partly responsible for the observed PD pathology. The host lab reported a dysfunctional type I interferon signaling is associated with PD, but the role of their receptor in PD is not yet understood. Here, we aimed to investigate the role of type I interferon (IFN) receptors, specially its soluble IFNAR2 receptor (sIFNAR2), in Parkinson’s disease (PD) pathology. Of note, the host lab has identified a new mutation in IFNAR1 associated with a family of PD patients, and I found that PD patients present lower serum levels of sIFNAR2 than healthy controls indicating dysregulation in this pathway. So, we hypothesize 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. Our objective was to investigate "in vivo" the potential actions of sIFNAR2 in regulating the IFNβ-signalling in the PD pathology and the neuroinflammatory context of the PD-model (IFNβ/IFNAR1KO).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания