Investigating how our brain cells speak in frontotemporal dementia
Dr Emma Clayton
King’s College London
1 April 2023 - 31 March 2027
Full project name:
Disrupted presynaptic proteostasis: a convergent pathomechanism for synaptopathy in frontotemporal dementia and amyotrophic lateral sclerosis
Frontotemporal dementia (FTD) and motor neurone disease (MND) are two brain diseases with overlapping causes. In both diseases, brain cells become damaged and can no longer communicate, and ultimately these cells die.
Our brain cells communicate through specialised connection points called synapses. Chemical signals are shared between synapses to coordinate many processes we do every day – like walking, talking, eating and thinking.
Previous research has shown that before brain cells die in diseases like FTD and MND, the synapses die first, which provides a target for researchers to study to develop our understanding of both conditions.
What will they do?
Dr Clayton and her team will use human cells and mice with features of FTD and MND to see the effects of a protein called TDP-43 on synapses ability to communicate.
They will look in detail at the protein interactions that can become disrupted in both diseases, importantly a molecular chain of events that enables a process called autophagy. This is the body’s way of clearing out damaged cells to then make new healthy cells in place.
The hope is that by understanding how these early processes are affected by FTD and MND, scientists can then tease apart the steps leading to damage to synapses and the death of cells.
What could the outcomes be?
This project will give researchers insight into a pathway that could be an earlier indicator of FTD and MND. By understanding what is happening deep within the brain, Dr Clayton could unlock new targets for future drugs.
There are limited treatments for FTD and MND, so opening up a new avenue to reveal new targets at this early stage of disease has the potential to be life-changing for people living with either disease.
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