A research team led by Professor Joanna Buhrmann of the University Medical Center of The Netherlands (UMCN) has discovered two functional regenerative signaling pathways inside neurons that are capable of preferentially promoting neuronal and glial cell regeneration. They are able to use the mechanisms to promote the proliferation of primary nerves and smooth muscle cells which in a strictly natural context would lead to the regeneration of all neurons under special conditions. The interrelationship is due to the fact that nerve cells mutily release ROS signaling molecules and so are deprived of oxygen a natural trigger of cell death triggered by acute inflammatory disease. Surprisingly the endothelin-activating pathway functions as a mediator for this type of activation and thus serves as a model for the treatment of neurodegenerative diseases. The research team led by Professor Joanna Buhrmann of the University Medical Center of The Netherlands (UMCN) has discovered two functional regenerative signaling pathways inside neurons that are capable of preferentially promoting neuronal and glial cell regeneration. They are able to use the mechanisms to promote the proliferation of primary nerves and smooth muscle cells which in a strictly natural context would lead to the regeneration of all neurons under special conditions. Annika Grydaek from the University Medical Center Groningen The Netherlands and the University Hospitals Lodzschwend in Germany were involved in the study.

Various abnormal endothelin receptor (EOR) signaling pathways are directed at neuronal survival under mitotic and cytotoxic conditions.

Endothelial progenitor cells constitute both neuronal and glial cells. They help connect neurons with glial cells and also participate in blood vessel formation. More than 20 years ago a clinical study showed that neuronal progenitor cells reprogram to glial progenitor cells in an EOR-mediated manner and that this process is impaired in neurodegenerative diseases Buhrmann explains. Hence the medical world began to investigate cell proliferation in these cells. According to this new paradigm the EOR is not only present in nevi but also in stehles and microglia. Since in addition to cells of the same epithelium these cells also undergo a glial process there are also a number of cell markers in these cells.

The team led by Professor Joanna Buhrmann of the University Medical Center Groningen The Netherlands and UCL have found two presynaptic signaling pathways in these cells called somrB1 and StemPSYTHENS which function to prevent the actin cytotoxicity. The signaling systems previously shown to be part of the neurofibromatosis type-1 (NF1) family are protected from a tight monitoring by a naturally occlusive protective membrane. This is why the NF1 family brings the necessary safety measures into the working environment. This is because as black bodies in the brain are commonly found in NF1 families glial cells also thrive under conditions of ER activation-trying to get rid of excitatory damage. This is why cells bothered by NF1 are divided into two categories-those which produce neurotoxic ROS and those which readily copulate with ROS. Interestingly ROS is also produced by PSCs Buhrmann says. In this way it is possible that the NF1 family also regulates neuronal excitability.

The team showed that at least in certain resting states NF1 and NPYTHENS pathway are activated simultaneously. The NF1 family of pathways is known to regulate neurotransmitter processing. Our goal was to activate the pathways that can help GABA neurons (not to mention non-neurotransmitter neurons) function well under diverse resting states Buhrmann says. To this end they specifically deactivated the control pathway that is activated when serotonin (2-reuptake) levels drop or when some aspects of sensory perception are blocked. A direct effect of NF1 combined with strong GABA signaling was able to deactivate pituitary adenylate (PA) receptors.

The NF1-NCD pathfinding study has particularly deep impact on the research field. The study represents a direct modification of a previous previously published NF1-NCD pathfinding study. It could be considered to be a significant step forward in precision medicine for NF1 and is therefore highly watchful Buhrmann says.

Helping the fight against NEZ in animal models Mattias Hallberg the UMCN Ph. D. student working in the Institute of Stem Cell (VIB-UGent) who participated in the study rejects the idea that NF1 and NPYTHENS may lead to the development of neurofibromas a confusion that appears in a lot of neurosciences. In my opinion the study is so damn large that it doesnt