Project EpiROM: Epigenetic reprogramming of microglia across neurodegenerative diseases

Basic data

Title:
EpiROM: Epigenetic reprogramming of microglia across neurodegenerative diseases
Duration:
01/02/2019 to 31/01/2022
Abstract / short description:
Neurodegenerative disorders are a growing socio-economic problem with no effective treatments in sight. Recent research indicates that inflammatory processes contribute significantly to the pathology of many neurodegenerative diseases. Therefore, it is crucial to understand how exactly the brain’s immune system affects neuropathology and whether environmental factors that change how the immune system responds could be risk factors for neurodegenerative diseases. Increasing evidence indicates that epigenetic changes, which occur in response to environmental factors, shape the immune response. Accordingly, we just demonstrated for the first time that inflammatory stimuli can trigger long-lasting epigenetic immune memory in microglia (the brain’s macrophages), which significantly impacts neuropathology in an Alzheimer’s model. Additionally, we found that microglia become epigenetically reprogrammed by Alzheimer’s pathology alone, driving a detrimental microglial phenotype. To determine whether these mechanisms are relevant across different neurodegenerative conditions, we now propose to profile the epigenome of microglia in Huntington and Parkinson’s disease models, where we will assess whether i) microglial epigenetic reprogramming occurs in response to brain pathology and ii) how the induction of epigenetic microglial reprogramming by environmental factors may modify disease pathogenesis. As epigenetic microglial reprogramming in these diseases remains completely unexplored, our results could lead to novel immuno-modulatory therapies for these devastating conditions.

Involved staff

Managers

Faculty of Medicine
University of Tübingen

Contact persons

University Department of Neurology
Hospitals and clinical institutes, Faculty of Medicine

Local organizational units

Institute of Medical Genetics and Applied Genomics
Department of Diagnostic Laboratory Medicine
Hospitals and clinical institutes, Faculty of Medicine

Funders

Stuttgart, Baden-Württemberg, Germany
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