Innovating Works

NEUROINFLAM-MS

Financiado
Proteomics of neuroinflammatory signaling: Illuminating cellular mechanisms driv...
Proteomics of neuroinflammatory signaling: Illuminating cellular mechanisms driving neurodegenerative diseases Alzheimer’s (AD) and Parkinson’s disease (PD) are prevalent neurodegenerative diseases, but their underlying mechanisms remain poorly understood. Emerging evidence suggests that neuroinflammation, characterized by the release of p... Alzheimer’s (AD) and Parkinson’s disease (PD) are prevalent neurodegenerative diseases, but their underlying mechanisms remain poorly understood. Emerging evidence suggests that neuroinflammation, characterized by the release of pro-inflammatory cytokines like IL-1β, TNF-α, and INF-γ, plays a pivotal role in these diseases, challenging the conventional focus on protein aggregates (Aβ, αSyn). In AD, it has been shown that elevated IL-1β levels induce the translocation of NEDD8 from the nucleus to the cytoplasm, where it co-localizes with the E3-ligase Parkin. Together with the kinase PINK1, Parkin is crucial for the removal of defective mitochondria, with loss-of-function mutations in these genes being the primary cause of early-onset PD. Intriguingly, phosphorylated NEDD8 can activate Parkin, implicating a more complex interconnection between neuroinflammation, NEDD8-and Parkin-regulated phosphorylation-dependent signaling in brain cells. Yet, a mechanistic understanding of cellular processes triggered by neuroinflammation remain elusive. This proposal aims to investigate spatiotemporal (phospho-)proteome changes in response to neuroinflammatory stress elicited by pro-inflammatory cytokines and αSyn fibrils. To achieve this, I will combine spatial-proteomics using subcellular fractionation and hybrid-DIA in combination with the cutting-edge Orbitrap Astral mass spectrometer. Initial analyses of neuronal cell line models will be extended in a second step to hPSC derived neurons, astrocytes, microglia, and co-cultures thereof. This enhances the translational relevance by mimicking neuroinflammation in the complex tissue architecture of the brain. Finally, bioinformatically shortlisted neuroinflammation-regulated proteins and phospho-sites will be validated in cell-based models. With this project, I aspire to unravel the cellular mechanisms underlying neuroinflammation, potentially unlocking new avenues for therapeutic strategies against neurodegenerative diseases. ver más
30/11/2026
UCPH
231K€
Perfil tecnológico estimado
Duración del proyecto: 30 meses Fecha Inicio: 2024-05-13
Fecha Fin: 2026-11-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-13
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023
Cerrada hace 1 año
Presupuesto El presupuesto total del proyecto asciende a 231K€
Líder del proyecto
KOBENHAVNS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5