How do protein clumps cause cell damage in neurodegenerative diseases?
Dr Francisco Iñesta-Vaquera
University of Dundee
1 November 2021 - 30 April 2023
Full project name:
Preclinical models to accelerate drug discovery in ALS/FTD
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neurone disease and approximately half of patients experience both movement problems and cognitive decline. There is no cure, due to our incomplete understanding of the disease.
Almost every person with ALS has clumps of a protein called TDP-43 and these clumps are linked to cell damage. Almost half of people with frontotemporal dementia (FTD) also have TDP-43 clumps in their brain cells. This suggests TDP-43 clump formation is a common feature across multiple diseases which cause cognitive decline.
Oxidative stress is a type of cell damage that occurs in neurodegenerative diseases. This process is linked with the build-up of TDP-43 in cells. However, researchers do not know exactly how TDP-43 clumps may trigger oxidative stress and which cells are most affected.
Dr Francisco Iñesta-Vaquera and colleagues will study TDP-43 clump formation in mice. They will track the TDP-43 proteins using a unique tag which will highlight where the TDP-43 clumps form and indicate which mouse cells undergo oxidative stress. Dr Iñesta-Vaquera’s team will monitor TDP-43 clump formation and oxidative stress in the mice at different ages. This will help the team to understand how TDP-43 influences cell damage and disease progression over time.
This project will provide an important model for understanding how diseases such as ALS and FTD progress. The findings of the project could also help in developing new drugs to block cell damage, leading to new possible treatments for neurodegenerative diseases.
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