Getting rid of junk: new ways for treating frontotemporal dementia
Researchers at the University of Salford are investigating the waste disposal system of brain cells in frontotemporal dementia.
Frontotemporal dementia (FTD) is associated with the build-up of toxic proteins in the brain. Understanding how and why these proteins accumulate differently in each individual with FTD is incredibly important. Normally, our cells use a waste disposal system to destroy abnormal and damaged proteins. This process is called ‘autophagy’ and goes awry in Alzheimer’s disease and Parkinson’s, contributing to the accumulation of toxic proteins.
No-one has yet investigated the role of autophagy in FTD, so Dr Lace-Costigan’s team is hoping to pave the way in this area of research. Investigating autophagy and its knock-on effects in this form of dementia will improve current understanding of the processes occurring during the course of the disease, and shed light on a potential way to tackle it.
Dr Lace-Costigan will try to understand whether some types of nerve cells are more susceptible to problems with autophagy than others. She will look specifically at those cells which regulate behaviour and personality, as these are widely affected in FTD. This could be incredibly important in helping to explain the varying symptoms seen in FTD, and uncovering different ways of treating the disease.
Dr Lace-Costigan’s team will use an array of techniques to understand why some parts of the brain are more susceptible to damage than others. This includes using human brain tissue, allowing the team to construct a clearer picture of the chain of events that leads to protein build-up and nerve cell damage. These clues could lead to a new approach in the development of drugs designed to intervene and stop the damage in its tracks.
Dr Lace-Costigan and her PhD student Richard Heale will take a close look at the cells waste disposal and recycling machinery, using human brain tissue from the Manchester Brain Bank, to probe how this system goes wrong in different forms of FTD. The researchers hope that drugs which could ‘kick-start’ this autophagy process could provide an effective approach to deal with the build-up of damaging proteins in FTD.
Richard will probe these important mechanisms in more detail, building up a picture of how the waste disposal system works in different parts of the brain and crucially, how it is altered in FTD compared to healthy people and those with Alzheimer’s. Together, they will tease apart why different groups of nerve cells are more prone to protein build-up than others, and use this knowledge to look at autophagy in cells in a dish.
They will also investigate whether boosting the process with drugs can help protect nerve cells. A range of experimental drugs designed to boost this waste disposal system already exists, so Richard can test these compounds on cells with specific waste disposal problems to examine their potential as new treatments for FTD. If promising, the student will move on to testing these experimental drugs in skin cells taken from patients, which have been turned into nerve cells in the laboratory.
Dr Gemma Lace-Costigan
University of Salford
1 October 2015 - 30 September 2018
Full project name
Alterations in autophagy in frontotemporal lobar degeneration: identifying new targets for therapeutic intervention