Our research Research by location and type University of Bath - Prof David Brown The molecular nature of how brain cells die What do we already know? Neurodegenerative diseases are associated with the death of brain cells. Many types of dementia and other diseases are related to abnormalities of particular proteins within the brain. For example, Alzheimer’s disease is associated with β-amyloid and tau, and Parkinson’s disease and dementia with Lewy bodies are associated with α-synuclein. Investigating how these proteins function normally, and what goes wrong in disease, will help us to understand the processes behind the progression of such conditions and the mechanisms by which cells die. What is this group trying to find out? The focus of Professor Brown’s research is to understand the molecular nature of how brain cells die. Whilst his group is especially interested some specific aspects of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and prion disease, what is especially interesting to them is what it is about the aging human brain that predisposes us to these diseases as we grow older. Something changes in the brain which alters how our brain cells can cope with differences in levels of certain proteins (e.g. α-synuclein and amyloid precursor protein) and the production of oxidative substances. Inducing age-related changes in microglia as a model for Alzheimer’s disease (PhD Studentship - Dafina Angelova)One of the cell types particularly important in maintaining the environment in the brain is microglia, which are part of the immune defence in the brain. Professor Brown’s group have developed a model of microglia that mimics the changes they undergo as the brain ages - by causing microglia to take up an excess of the metal iron their behaviour is changed. Current research is looking at how microglia treated in this way alter processes associated with diseases like Alzheimer’s disease. Α-synuclein and cellular iron reduction (jointly funded by Alzheimer’s Research UK)The group is also interested in proteins associated with neurodegeneration such as the amyloid precursor protein (APP, which is cleaved to form β-amyloid) and α-synuclein. While these proteins change in diseases and behave abnormally, they do have a different activity in healthy cells. Previous studies by the group have studied the protein α-synuclein and determined that it has a function that alters the way the metal iron is handled by cells, by causing iron to be converted to a form more active in cells. They are determining whether this activity is important to healthy cells and whether this is changed in diseases like Parkinson’s disease. Α-synuclein expression regulates the breakdown of amyloid precursor protein (PhD Studentship - Hazel Roberts)They have also recently shown that α-synuclein changes the rate of formation of β-amyloid, a protein normally associated with Alzheimer’s disease. They are currently determining the mechanism of α-synuclein activity in this regard. The potential cross-over between these proteins may be of great importance in understanding cellular processes that change as our brain ages. How do they do this? They use a combination of molecular biology and biochemistry techniques with cell lines, primary cell cultures and human post-mortem brain tissue donated to brain banks. Why is it important? If we know more about the cellular mechanisms which go wrong in disease, it will identify targets which may be utilised to alter disease progression and allow more effective drugs to be developed. Please click here for more information about the work of Professor David Brown.