Summary

Dr Helen Waller-Evans and her research team are looking at targeting a protein called TRPML1 as a possible new treatment for Alzheimer’s disease. 

What do we already know?

There are parts of the cell called lysosomes that function as the cells recycling centre, breaking down proteins so they can be reused. TRPML1 is a protein inside these lysosomes. When activated, TRPML1 allows amyloid to move into the lysosome. Amyloid is a molecule in the brain which is often linked with the cognitive decline seen in Alzheimer’s disease. 

In Alzheimer’s disease, the activity of TRPML1 is increased and lots of amyloid moves into the lysosome and gets broken down incorrectly. This can lead to the build-up of toxic fragments called amyloid beta. This build-up of amyloid beta limits communication between brain cells and can cause them to die. It is a key component in the development of Alzheimer’s disease.  

What is this project trying to find out?

Dr Helen Waller Evans and her team think that if they can reduce the activity of TRPML1, they could reduce the build-up of amyloid beta and slow the progression of Alzheimer’s disease. They will test this using a variety of small molecules that target TRPML1 in different ways. When they find the compound that has the biggest impact on TRPML1, they will then look at how good it would be at treating Alzheimer’s disease in patients. 

Before looking at the activity of TRPML1, Dr Waller-Evans and her team aim to develop a new tool which can speed up this process, increasing the efficiency of future research. 

Why is this important?  

If successful, this research will identify a new drug-like molecule that can be further developed as a treatment for Alzheimer’s disease and other forms of dementia.

What has been achieved so far?

To understand how molecules like amyloid move inside cells and assess the effects of drug treatments, researchers traditionally need to manually examine hundreds of images. This process is time-consuming and slows down research progress. It is a long and labour-intensive process that can slow down research. 

Dr Helen Waller-Evanas and her team with the help of Sian Gardiner have developed a new tool which will hugely speed up research. It allows scientists to examine multiple conditions and cell types together. For instance, in this study, 12 different types of cells were looked at to understand the impact of dementia at the cellular level.  

The team now plans use this technology to see if drug treatments can reduce the effects of dementia on cells.