Unravelling how inflammation may worsen the diseases that cause dementia
Professor Maria Grazia Spillantini
University of Cambridge
1 March 2022 - 31 August 2023
Full project name:
Extracellular matrix remodelling and metalloproteases in tauopathies
What does the project aim to do?
The tau protein is found in all our brains and helps with the structure and support of our cells. In some of the diseases that cause dementia, such as Alzheimer’s and dementia with Lewy bodies, tau protein behaves differently and starts to form tangles in our brains. This leads to damage to the connections between nerve cells and inflammation in the brain.
Our brain’s immune cells, microglia, are on hand to protect the brain and keep connections between our cells healthy. When we get a build-up of tau though, our microglia remove cells with these tangles, and this can cause more harm than good.
When microglia remove tau cells, they can end up releasing a number of components back into the brain. One of these is an enzyme called MMP3 and this can upset the delicate balance of cells and proteins we have in our brain environment.
Prof Spillantini and her team want to study MMP3 to see what affect it has on the brain and whether it worsens damage in people with tau build-up caused by disease.
What will they do?
The team will be identifying the different enzymes that are released when microglia clears away tau brain cells, and then looking at where these enzymes are found. They will then look at what these enzymes break down and how this effects the brain environment.
Researchers will compare microglia and nerve cells from mice with tau build-up and healthy mice. They will also use cutting-edge technology to grow mini brains in the lab from cells of people living with a disease involving tau tangles.
This Pilot Project will provide the initial results to show whether MMPs and other enzymes are important in the pathology of tau diseases. Findings can then be the basis for future studies to further understand their effects and potential as biomarkers for disease.
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