Linking cholesterol metabolism in myeloid cells to remyelination in mice and humans

B07

This project addresses a fundamental question in the field of multiple sclerosis, namely why remyelination mostly fails in progressive MS. Myeloid cells are the dominating inflammatory cell population in active and mixed active/inactive MS lesions. Our recent animal experiments demonstrated that accumulation of myelin debris in myeloid cells can induce a maladaptive immune response that impedes remyelinationm. Yet the mechanisms underlying the block of myelin repair are unknown. We want to understand how different functional states of myeloid cells are linked to oligodendrocytes and remyelination in MS lesions. These are our main questions::

    1. How does cholesterol clearance in phagocytes affect oligodendrocytes and remyelination in demyelinating animal models?
    2. Are lipidated particles that are formed after myelin debris clearance reutilized by oligodendrocytes and required for remyelination?
    3. How do supernatants from phagocytes at different stages of cholesterol clearance affect oligodendroglial differentiation, migration, myelination or cell death? What are the underlying molecular mechanisms?
    4. Do supernatants from phagocytes at different stages of cholesterol clearance induce cellular senescence in oligodendrocytes?
    5. Are different stages of cholesterol clearance associated with lesion activity or ongoing or impaired remyelination?

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigators:

Univ.-Prof. Dr. med. Tanja Kuhlmann
Institut für Neuropathologie
Münster
tanja.kuhlmann@ukmuenster.de

Prof. Dr. med. Mikael Simons
Institut für Neuronale Zellbiologie
TU München
msimons@gwdg.de

News

Wed, 22/11/2023
Hybrid seminar on ‘The origins and consequences of multiple slerosis’
Munich. Prof. Lars Fugger from the Nuffield Department of Clinical Neurosciences at the University of Oxford will give a hybrid seminar on ‘The origins and consequences of multiple slerosis’ in the large auditorium at the TranslaTUM in MUNICH. The talk is organized by the TRR 355 and will be streamed via the TRR 355 seminar […]...more
Wed, 23/08/2023
Neurology Webinar on human brain T cells in health and multiple sclerosis
Muenster. The SFB 128 is happy welcome Joost J.F.M. Smolders, MD, PhD , head of MS Center ErasMS and Neuroimmunology Brain (NIB) Research Group at the Department of Immunology of the Erasmus University Medical Center (Erasmus MC), as lecturer at the Muenster Neurology Webinar. His talk is entitled “Unique features of human brain T cells […]...more
Thu, 03/08/2023
New Date: Neurology Webinar – How much gut needs the brain
Muenster. In January 2024, Prof. Anne-Katrin Pröbstel, Head of the Interdisciplinary Autoimmune Clinic at the University Hospital of Basel, will visit Muenster to give insights into the microbiota-immune crosstalk in neuroonflammation. Her presentation – which ois part of the Muenster Neurology Webinar – will be live-streamed. Time: Wednesday, January 24, 2024 Place: Online at zoom. […]...more