Summary: The findings may have implications for new avenues of research into various neurodegenerative diseases, including ALS and Alzheimer’s.

Source: University of Bath

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 UK.

This discovery focuses on a molecule that plays an important role in nerve cell development and is known to contribute to disease when it goes wrong.

Previously, it was thought that this molecule was limited 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 the previous results obtained by the same group. It is found in the cytoplasm (the watery interior of the cell).

The study shows for the first time that the cytoplasmic pool of this protein is functional.

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

The discovery is described in Current biology It was developed by Professor Corinne Huart at King’s College London, working with Dr Nicolas Nicolaou in the Life Sciences Department.

Loss of nerve function

Scientists know that over a period of time, proteins – the molecules studied in this study – can sometimes be combined in the cell cytoplasm and form insoluble compounds, and these compounds can interfere with the function of the nerve cell (neuron cell) and eventually lead to the formation of a neuron. Loss of function and deterioration.

But this study is the first to show that a large splicing protein is found in protein/messenger RNA complexes (known as RNA granules) in the spindles of neurons.

Axons are long projections that carry electrical impulses away from the nerve cell body, connecting neurons to neighboring neurons, or transmitting information from neurons to tissue in the body (muscle or skin).

Axon dysfunction is known to be the cause of many progressive neurodegenerative diseases, so the presence of a protein in this neuron cell segment suggests a possible mechanism of disease.

Modeling the messenger RNA molecule

The researchers discovered that the spliced ​​protein SNRNP70 binds to messenger RNA (mRNA) strands and subsequently forms a conformation. These strands carry the genetic information from the DNA in the cell nucleus to the cell cytoplasm.

The information carried by mRNA is used to create more proteins, the building blocks of life. The team also found that a splicing protein is required for the mRNA to move from the axon of the neuron to the other parts of the neuron.

watch out

This shows the weight of the hand
This shows the motor neurons
Section of zebrafish trunk. Motor neurons (green) send axons that enter muscle fibers (red). Credit: Nikolas Nikolaou

Speaking about research using zebrafish as a genetic model system, Dr. Nicolaou said: “When we interfered with protein assembly, we observed that motor neurons did not develop properly. They failed to form relationships where they should have, and lost other important relationships. This type of behavior is also observed in human neurodegeneration.

“However, when SNRNP70 was reintroduced into the cytoplasm and axons of these neurons alone, it was sufficient to restore motor connectivity and neuronal function.”

Despite being a small freshwater fish, the zebrafish has a nervous system similar to that found in humans.

In the next part of this research, Dr. Nicolaou plans to explore the exact function of this protein in axons. We know that proteins bind to other proteins, so which proteins does this molecule bind to? And what happens when we remove these complexes from the cytoplasm – how does this affect the function of neurons?

He added, “Now that we know that these types of molecules have functions outside the nucleus, we must approach the nucleus from a different angle by asking ourselves how these pathogenic compounds interfere with the function of these proteins, not only in the nucleus.” Also in the cytoplasm, and what role do they play in the degeneration of neurons. This is something that has not been thought of before.”

So neuroscience research news

Author: Chris Melvin
Source: University of Bath
Contact: Chris Melvin – University of Bath
Image: The image is credited to Nicolas Nicolaus

Preliminary study: The findings are shown in Current biology

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