This is a Discovery Research Grant awarded to Dr Benjamin Delprat at the Université de Montpellier, France, in 2024.
Background
Every cell in the body is made up of different compartments and can be thought of like a city. The nucleus (which contains all the genes that run the cell) is the town hall, the cytoskeleton (a network of proteins which link different parts of the cell together) is the transport network, the endoplasmic reticulum (which makes all the proteins that the cell needs) is the manufacturing district and the mitochondria (which produce the energy that the cell needs to function) are the power stations.
All of these parts are connected to each other and need to communicate with each other to ensure the city runs properly and the same is true of cells.
One of the most important connections is between the endoplasmic reticulum and the mitochondria. If this connection is damaged or stops working, it can lead to the death of the cell. This is what happens in many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and motor neurone disease.
Another rare neurodegenerative inherited disease, Wolfram syndrome, is also linked to problems with the communication between endoplasmic reticulum and mitochondria. Wolfram syndrome is characterised by sensorineural hearing loss, vision problems, diabetes and other neurological problems. The gene that is linked to Wolfram syndrome, WFS1, is also linked to other forms of inherited hearing loss.
More recently, evidence has suggested that cisplatin, an anti-cancer drug which can cause hearing loss as a side effect by damaging hair cells in the cochlea, may do so by blocking this cellular communication.
Aim
Data from the Delprat lab has shown that it is possible to restore communication between the endoplasmic reticulum and mitochondria by targeting a protein involved in the process, called the sigma-1 receptor, with drug molecules that activate it. The aim of the researchers is to investigate whether targeting this protein can protect hair cells from the damaging effects of cisplatin treatment.
Benefit
The results from this project could ultimately lead to a treatment that can protect people’s hearing when they have to undergo cisplatin chemotherapy.