New WCMR Progress Meeting Series

We are delighted that our WCMR Progress Meetings are back for 2022/23!  These meetings are a fantastic opportunity for our team to get together (in person, at last!) and share research updates or highlights from recent conferences that team members have attended. The main purpose of this is to stimulate discussion and nurture our collaborative approach to transforming the lives of those affected by mitochondrial disease and dysfunction.

In our first meeting of the series, we heard from Dr Helen Devine and Dr Daniel Erskine who both talked about their research that highlights the important role that mitochondria play in many conditions, including neurodegenerative diseases.

Dr Helen Devine

The title of the first talk was ‘Mitochondria in neurodegeneration: What can we learn from a human stem cell model of motor neuron disease?’. In this presentation, Helen described how she is using stem cells from patients with genetic motor neuron disease to try and investigate how and why the mitochondria stop working properly in neurodegeneration.

The second talk was given by Dr Daniel Erskine, who is an Alzheimer’s Research UK Senior Fellow and Senior Lecturer in Neurodegenerative Pathology. Read on to find out more from Dan.

Understanding the Role of Alpha-synuclein in Neurodegenerative Diseases.

Lewy body disease (LBD), is an umbrella term for a group of neurodegenerative diseases that includes Parkinson’s disease and dementia with Lewy bodies. These diseases are termed LBD because their brain cells contain accumulations of a protein called alpha-synuclein when examined post-mortem. The general view held by many scientists is that Lewy bodies are harmful, yet no studies have examined whether this is the case. Our studies have been focused on trying to understand why Lewy bodies occur and how they affect brain cells in which they form. This work is important as most drugs in development for LBD target alpha-synuclein so it is critical we are sure it is the best target.

Dr Daniel Erskine

Understanding alpha-synuclein has been made difficult due to differences between mouse and human alpha-synuclein. This is why we have developed a unique system where human brain tissue from patients undergoing brain surgery, with consent of the patients, is kept alive in our laboratory instead of being destroyed, enabling us to study alpha-synuclein in real living human brain tissue. These studies have identified alpha-synuclein seems to be associated with damage to mitochondria, the parts of brain cells responsible for generating energy, but we were unable to study Lewy bodies as it is not currently possible to generate them in the laboratory. When we studied mitochondria in post-mortem LBD brain tissue we found they were abnormal but, surprisingly, cells with Lewy bodies had apparently healthier mitochondria than brain cells without Lewy bodies. A study by researchers in Amsterdam has demonstrated that Lewy bodies also contain damaged mitochondria, in addition to alpha-synuclein, which led us to wonder whether Lewy bodies might be acting like a bin for damaged parts of cells when they can’t be disposed using normal processes.

Our ongoing work is examining how brain cells dispose of waste in LBD, with a particular focus on mitochondria. This work has important implications for understanding what causes LBD and the role of Lewy bodies in this condition, with important implications for developing new treatments. To expand on this line of work, we are also investigating mechanisms in conditions caused by difficulties disposing of waste in brain cells, including conditions that typically affect children such as Krabbe disease and metachromatic leukodystrophy.

To find out more about Dan’s research, click here.