Could misplaced ribonuclear proteins play a role in Alzheimer’s?

Research project: Do heterogeneous ribonuclear proteins play a role in the pathogenesis of Alzheimer’s disease?

Lead Investigator: Professor John Hardy

  • Institution: University College London
  • Grant type: Project
  • Duration: 36 months
  • Amount: £379,161

Why did we fund this project?

Comments from our Research Network volunteers:

‘Particularly significant to me and my family is the potential to identify previously undiscovered pathways that could be used in the treatment of Alzheimer’s disease and other forms of dementia.’

Project summary

Ribonuclear proteins are bundles of genetic information and proteins that normally live inside the control centre of brain cells. These researchers are set to find out whether these proteins help to protect the brain and whether their misplacement in Alzheimer’s starts or makes the disease worse.

The background

Inside brain cells there is a control centre known as a nucleus. The nucleus holds all the genetic information of the cell and controls the production of most of the proteins needed for the cell to function. Scientists have discovered strange bundles of genetic information and proteins inside the nucleus. Up until now, very little has been understood about these bundles which are known by the catchy name ‘heterogeneous ribonuclear proteins’.

Professor Hardy and his research colleagues had noticed that these ribonuclear proteins are disorganised in the brains of people with Alzheimer’s disease. Instead of being inside the nucleus they found ribonuclear proteins in the outer part of the cell, called the cytoplasm.

The researchers suspect that ribonuclear proteins work in healthy brain to protect brain cells. In Alzheimer’s they become misplaced outside the nucleus and can’t perform their protective role. This may contribute to or worsen the development of Alzheimer’s disease.

What does this project involve?

Professor Hardy and colleagues will begin by using brain tissue that has been donated to research by people who died with Alzheimer’s disease and people who died without a brain disease. 

They will closely examine the ribonuclear proteins in the brain cells to confirm firstly that there is misplacement of these proteins in Alzheimer’s. Secondly they will find out whether certain groups of brain cells have more misplacement of these proteins than others. This could help to explain why certain groups of brain cells are more vulnerable to Alzheimer’s disease than others.

Like careful detectives they will next they will look at other proteins that ribonuclear proteins interact with. They will aim to understand whether the misplacement of ribonuclear proteins leads to a chain reaction of dysfunction through other proteins.

To back up their research using human brain tissue, the researchers will also grow brain cells in a dish. They will treat these brain cells with different chemicals and expose them to proteins to replicate the conditions of the disease. This will allow them to find out how the ribonuclear proteins react.

How will this project help people with dementia?

This project will find out for the first time whether these ribonuclear proteins might play a role in protecting brain cells against Alzheimer’s disease. If that is the case then they might be a good target for future drug treatments. 

This is early stage research but it is a quickly developing field that is building a new path towards future discoveries that could help to improve the lives of people with dementia.

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