Project iCA_08-01_2020: Cyathanes as neutotrophin-inducing host specific anti-infectiva against S. aureus

The medicinal mushroom Hericium Erinaceus is known to produce secondary metabolites with neurotrophin-inducing properties. One of those secondary metabolites is cyathane diterpenoid erinacine C (EC). Incubation with EC induces the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in astrocytoma cells which are important modulators for neuronal survival and differentiation.

 

The medicinal mushroom Hericium Erinaceus is known to produce secondary metabolites with neurotrophin-inducing properties.
One of those secondary metabolites is cyathane diterpenoid erinacine C (EC). Incubation with EC induces the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in astrocytoma cells[1] which are important modulators for neuronal survival and differentiation.

Recent studies showed that NGF is expressed and secreted in macrophages as part of the immune answer after S. aureus infection, this leads to activation and accumulation/recruitment of neutrophils.[2]
It could also be shown that EC induces anti-inflammatory effects in microglial cells, the brain resident macrophage cells. These results lead to the assumption that EC not only holds neuroprotective but also immuno-modulating properties and potentially supports/activates the innate immune system.

For this project Cellular and Molecular Neurobiology provides the optimal conditions to study both, the regulatory mechanism in vitro in cell culture as well as with zebrafish, as an optimal model organism, to study the immunomodulating mechanism in vivo.

To identify the regulatory mechanism of NGF expression, dominant-negative transcription factors are used to suppress the EC-mediated NGF expression. This identification would allow the construction of an EC-sensitive sensor that visualizes and verifies the EC-mediated expression of NGF in zebrafish.

The transparent nature of zebrafish allows using of zebrafish in fluorescence-based inflammation assays which facilitates the quantification of inflammation and with that the possibility to verify the anti-inflammatory properties of EC.

Name of Doctoral Researcher
Sven Hoffmeister

Name of Supervisor
Prof. Dr. Reinhard Köster

Institute / Department
Cellular and Molecular Neurobiology, TU Braunschweig

Contact details
sven.hoffmeister@tu-bs.de


[1]Rascher, M.; Wittstein, K.; Winter, B.; Rupcic, Z.; Wolf-Asseburg, A.; Stadler, M.; Köster, R.W. Biomolecules 202010, 1440.

[2] Hepburn L. et al. Science, 2014, 346, 641-646.