The discovery of nerve cells may improve treatment options for patients with neurodegenerative diseases
A discovery that could improve treatment options for patients with neurodegenerative diseases has been made by scientists at King's College London and the University of Bath in the United Kingdom. This finding focuses on a molecule that plays an important role in nerve cell development and is known to contribute to disease when it malfunctions. This molecule was previously thought to be restricted to the cell nucleus (the organelle that contains a cell's DNA and is separated from the rest of the cell by a membrane), but this new study confirms previous findings by the same team that this is also possible...

The discovery of nerve cells may improve treatment options for patients with neurodegenerative diseases
A discovery that could improve treatment options for patients with neurodegenerative diseases has been made by scientists at King's College London and the University of Bath in the United Kingdom.
This finding focuses on a molecule that plays an important role in nerve cell development and is known to contribute to disease when it malfunctions. This molecule was previously thought to be restricted to the nucleus (the organelle that contains a cell's DNA and is separated from the rest of the cell by a membrane), but this new study confirms previous findings by the same team that it can also be found in the cytoplasm (watery interior of a cell). The study also shows for the first time that the cytoplasmic pool of this protein is functionally active.
This finding has important implications for research into neurodegenerative diseases such as Alzheimer's and motor neuron disease.
The discovery, described in Current Biology, was made by Professor Corinne Houart at King's College London in collaboration with Dr. Nikolas Nikolaou from the Department of Life Sciences in 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's cytoplasm, and that these complexes can disrupt the function of a neuron (nerve cell), ultimately causing the neuron to lose function and degenerate. However, this study is the first to show that a key splicing protein can be found within protein/messenger RNA complexes (known as RNA granules) within the axons of nerve cells.
Axons are the long projections that conduct electrical impulses away from the body of the nerve cell, connect neurons to neighboring neurons, or transmit information from neurons to tissues in the body (e.g., muscles or skin). Axon dysfunction is known to be the cause of many progressive neurological disorders, so the discovery of splicing proteins in this part of the nerve cell provides clues to the mechanism that could lead to disease.
Formation of the messenger RNA molecule
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The researchers found that the splicing protein SNRNP70 binds to messenger RNA (mRNA) strands and then shapes them. These strands carry genetic information from the DNA in the nucleus to the cell's cytoplasm. The information in the mRNA creates other proteins, the building blocks of life. The team also discovered that the splicing protein is needed for mRNA to move from the body of the nerve cell along the axons to more peripheral parts of a neuron.
Commenting on this research, which uses zebrafish as a genetic model system, Dr. Nikolaou: "When we interfered with the function of the splicing protein, we saw that motor neurons did not form well, and they lost other important connections. This type of behavior is also observed in human neurodegeneration. However, when SNRNP70 was reintroduced only into the cytoplasm and axons of these neurons, it was enough to restore motor connectivity and neuronal to restore function.”
Despite being a small freshwater fish, the zebrafish is a species with a nervous system remarkably similar to that of humans.
In the next phase of this research, Dr. Nikolaou to research the exact function of this protein in axons. "We know that proteins interact with other proteins, so which 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 need to approach neurodegeneration from a different angle and ask ourselves how these disease-causing aggregates affect the function of these proteins not only in the nucleus but also in the cytoplasm and what role they play in the breakdown of neurons. This is something that hasn’t been thought about before.”
Dr. Nikolas Nikolaou, Department of Biological Sciences, University of Bath
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Reference:
Nikolaou, N., et al. (2022) Cytoplasmic pool of the U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity. Current Biology. doi.org/10.1016/j.cub.2022.10.048.
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