Neurodegenerative diseases are chronic, progressive, and incurable. They affect the central nervous system. Today, there are only treatments available that only relieve the symptoms and are not effective for all patients. Researchers at Heidelberg University in Germany are working on a new therapeutic approach. They explain it in a study published in the journal Science.
Protective receptors that become destructive
The research team was interested in the process of neurodegeneration: the death of cells in the nervous system. In the brains of the laboratory mice, they analyzed the role of the N-methyl-D-aspartate receptor (NMDA receptor): it is activated by glutamate, a neurotransmitter, and allows calcium to enter the cells. This receptor plays a key role because it is located at a connection point between different neurons, the so-called synapse, which is important for memory and the learning process. But some of these receptors are located outside of these areas and when they become active, they can cause cell death. If there is no pathology, the organism prevents the activation of these receptors, but in the case of degeneration, this is no longer the case. The NMDA receptor changes from a protective role inside the synapses to a destructive role outside the synapses. “They change from Dr. Jekyll to Mr. Hyde,” the researchers said.
Worked on mice
For Hilmar Bading, the lead investigator of the study, it is clear that the toxic properties of the NMDA receptor play a “central role in many neurogenerative diseases”, in particular Alzheimer’s and Charcot’s disease. “Understanding why NMDA receptors located outside synapses lead to cell death is of paramount importance for the development of neuroprotective therapies”. Analyses performed in mice have shown that a protein called TRPM4 transfers these toxic properties to NMDA receptors. Together with their team, they found an inhibitor, a so-called “interface inhibitor”, which is able to break the bond formed between the receptor and the protein and thus prevent the phenomenon of cell death. The test performed on animals has proven its effectiveness and gives the researchers hope for curative treatments for neurodegenerative diseases. “However, it will take several more years to obtain approval as a human drug, as this new substance will first have to go through several stages of pre-clinical and clinical trials,” the researcher concludes.
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