The discovery of neurons could improve treatment options for patients with neurodegenerative diseases

Scientists from King’s College London and the University of Bath, UK, have made a discovery that could improve treatment options for patients with neurodegenerative diseases.

This discovery concerns a molecule that plays an important role in the development of nerve cells and is known to contribute to disease when it malfunctions. Previously, this molecule was thought to be restricted to the cell nucleus (the organelle that contains the cell’s DNA and is separated from the rest of the cell by a membrane), but this new study confirms an earlier discovery made by the same team accordingly that it can also be found in the cytoplasm (the inner part). cell water). The study also demonstrates for the first time that the cytoplasmic assembly of this protein is functionally active.

This finding has important implications for research into neurodegenerative disorders such as Alzheimer’s disease and motor neurone disease.

The discovery described in Current Biology It was carried out by Professor Corinne Howart from King’s College London, in collaboration with Dr Nicholas Nicolau from the Department of Life Sciences, Bath.

loss of nerve function

Scientists have known for some time that splicing proteins — the molecules studied in this research — can sometimes aggregate and form insoluble complexes in the cell cytoplasm, and that these complexes can interfere with the function of a neuron (nerve cell), ultimately resulting in Loss of function and neuronal degeneration. However, this study is the first to show that a master splicing protein can be found in protein/messenger RNA complexes (known as RNA granules), in the axons of neurons.

Axons are the long projections that transmit electrical impulses from the nerve cell body, connect neurons to neighboring neurons or transmit information from neurons to body tissues (for example, muscles or skin). Axonal dysfunction is known to cause many progressive neurological disorders. The discovery of splicing proteins in this part of the neuron gives a clue as to the mechanism that could be at the origin of the disease.

Formation of mRNA molecule

The researchers found that the binding protein SNRNP70 binds to and then forms strands of messenger RNA (mRNA). These strands carry genetic information from the DNA in the cell’s nucleus to the cell’s cytoplasm. The information carried by mRNA is used to create other proteins, which are the building blocks of life. The team also found that the splicing protein is necessary for mRNA to travel from the nerve cell body along axons to the terminal parts of neurons.

Commenting on the research, which uses zebrafish as a genetic model system, Dr. Nicolau said, “When we interfered with the splicing protein, we found that it had no effect on the nervous system.” When we interfered with the splicing protein’s function, we found that the motor neurons were not forming properly. They failed to make the connections where they should have, and they missed out on other important connections. This type of behavior is also seen in human neurodegeneration. However, when only SNRNP70 was reintroduced into the cytoplasm and axons of these neurons, it was sufficient to restore motor connectivity and neuronal function again. “

Although zebrafish are small freshwater fish, they are a species whose nervous system is remarkably similar to that of humans.

In the next phase of this research, Dr. Nicolau plans to explore the precise function of this protein in axons. We know that proteins interact with other proteins, so what proteins does this molecule interact with? And what happens when we remove these complexes from the cytoplasm – how does that affect neuron function? »

Now that we know that these types of molecules have a function outside the nucleus, we will have to approach neurodegeneration from a different angle, asking ourselves how these pathogenic aggregates interfere with the function of these proteins not only in the nucleus but also in the cytoplasm, and what role do they play in neuronal degeneration. This is a question we haven’t considered before. »

Dr Nicholas Nicolau, Department of Life Sciences, University of Bath.