Magnetic nanoparticles raise hopes for cures for Parkinson’s.
One reason why nerve damage to the brain cannot be easily regenerated is that neurites do not know in which direction they should develop. A team of researchers from the Ruhr-Universität Bochum (RUB), the Sorbonne University Paris and the Technische Universität Braunschweig are now working to show them the direction using magnetic nanoparticles.
The team, led by Professor Rolf Heumann, Senior Molecular Neurochemistry Researcher at RUB, hopes this will help alleviate the long-term effects of neurodegenerative diseases such as Parkinson’s. The results of the work were published on December 31, 2020 in the journal Scientific reports.
Neurites do not know how
Restoring brain function after injury or due to neurodegenerative diseases remains an unsolved problem in neuroscience and medicine. Regeneration in the central nervous system is only possible to a very limited degree, as regenerative neuritis, the axon, comes in contact with proteins that have growth-inhibiting properties. “The regenerative axis also does not initially know in which direction it must develop to reach and functionally connect the regenerated target tissue,” explains Rolf Heumann.
The signaling pathway allows nerve fibers to grow
The team at Bochum was previously able to show that activating a central signaling pathway within neurons, caused by the Ras membrane protein that binds to the cell membrane, protects cells from degeneration and also leads to fiber growth. The researchers wanted to test the direction of fiber growth in the current project. To do this, they used magnetic nanoparticles, which were implanted into neuron models. Activation of the Ras signaling pathway is activated by a permanently active Ras protein or by a Ras regulator switch protein.
Control of nanoparticles with magnetic ends
“We first showed that we were able to move iron nanoparticles into neurons in a controlled way using magnetic ends,” explains Fabian Raudzus. The team then also managed to bind the Ras regulator switch protein inside the cell to the nanoparticles and transfer them magnetically to the cell membrane. The researchers were then able to implant these functional nanoparticles into the neurite and allow it to accumulate at its tip, which determines the direction of growth. The binding of the nanoparticles and the Ras switch protein was demonstrated using light scattering measurements and by microscopic procedures such as fluorescence correlation spectroscopy.
The research team sees therapeutic potential in the ability to magnetically activate activated nanoparticles in nerve fibers: “Japanese researcher Professor Jun Takahashi recently launched a clinical trial based on transplantation of adapted neurons to replace certain dopamine . “The long-term goal of our study is to promote the regeneration of transplanted dopaminergic neurons using functional magnetic nanoparticles in the brain.”
Supplying several million neurons
To achieve this, nanoparticles must be inserted into several million neurons. The team was able to demonstrate using model cells that large populations of cells were loaded simultaneously with these magnetic nanoparticles using a simple mechanical pressure-based method. This did not stop the induction of nerve fiber growth.
“Although we are still far from a clinical application, we hope that our experiments represent a first step in supporting the regeneration of transplanted dopaminergic neurons in the treatment of Parkinson’s,” says Rolf Heumann.
Raudzus, F., et al. (2020) Magnetic spatio-temporal control of SOS1-conjugated nanoparticles for guided neurite growth in dopaminergic single cells. Scientific reports. doi.org/10.1038/s41598-020-80253-w.