Sphingosine-1-phosphate-receptor modulation

The primary focus of our current research is on oligodendrocyte pathologies, the sphingosine-1-phosphate receptor (S1PR) system, and how this system is modulated by established pharmaceuticals, particularly Siponimod. We hypothesize that in diseases like multiple sclerosis, central cytoprotective effects of S1PR modulators, such as Siponimod, are mainly mediated through agonistic interactions with the S1PR5 receptor subtype. Oligodendrocytes, which express this receptor subtype at high levels, may be protected from cellular stress, degeneration, and demyelination as a result. Our central animal model for this research is the cuprizone model, which allows us to study pronounced oligodendrogliopathy, subsequent demyelination, glial cell activation, and immune cell recruitment in a non-autoimmune context. We use clinically established drugs (e.g., Siponimod) and various (conditional) mouse mutants in our investigations. The research is conducted on both murine and human brain tissue, employing established laboratory techniques such as paraffin and cryosectioning, immunohistochemistry, fluorescence microscopy, serial section scanning electron microscopy, and real-time PCR.

Working on this project:

• cand. med. Emil Pril