Loss of neurotrophic factors in neurodegenerative dementias: Back to the crossroads of proteins

In an international collaboration, our group at the MPI-P in Mainz works together with teams from Italy, Great Britain, Belgium and the USA on an approach for neurodegenerative disease therapy. On the one hand, the goal is to understand the processes occurring in the brain that lead to the diseases; on the other hand, the development of a method for targeted drug delivery.

In the human brain, neurons are responsible for the transmission of electrical signals. They form the functional component responsible for sensations, stimuli and memories. In the presence of dementia, there is an accumulation of proteins outside the neurons, which then leads to the death of the neuronal cells. How to prevent the death of neurons is still the subject of scientific research today. In a recent transnational research project (EU Joint Program on Neurodegenerative Disease Research (JPND)), which is funded in Germany by the German Federal Ministry of Education and Research (BMBF), researchers are now trying to address this question.

While project partners in Italy, Great Britain, Belgium and the USA investigate the exact processes in the brain, the MPI-P explores methods to transport drugs. Overcoming the blood-brain barrier represents the main challenge. Drugs to be used in the brain must be able to pass this barrier first before acting in the brain. For this purpose, our group is working on nanocapsules that can overcome the barrier. On the one hand, it has to be taken care that the nanocapsules have a long circulation time in the blood in order to increase the probability of interaction with the target cells in the affected brain areas. For this, it is important to design the nanocapsules so that they are not directly excreted by the kidney or liver. On the other hand, special targeting groups - consisting of proteins - must be placed on the capsule surface in order to be recognized and absorbed by the target cells.

The partners involved in the project are examining the exact processes in the brain in parallel with the development of the transport system in Mainz. Here, exosomes and neurotrophic factors are of major interest. Exosomes are small compartments released by cells to communicate with each other. At the same time, neurotrophic factors are biochemical messengers responsible for the growth and survival of nerve cells. The interaction of exosomes and neuron-stimulating factors is seen as the main focus for the understanding of dementia by researchers.

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