Parkinson’s disease is a progressive, degenerative brain disease that causes trembling, stiffness, slowness of movement and a loss of fine motor control.
The disease destroys neurons in an area of the brain called the substantia nigra. Without these dopamine-producing cells, the brain’s ability to control movement is progressively reduced.
We are conducting research to improve diagnosis of Parkinson’s disease and gain a better understanding of the mechanisms that cause the disease.
Symptoms of Parkinson’s disease are caused by a gradual deterioration and death of brain cells in the substantia nigra. However, people with Parkinson’s can lose up to 70% of susceptible brain cells and go on for many years before symptoms become noticeable.
While symptoms vary from person to person, the most well-known symptom is a tremor. People with Parkinson’s disease may also experience slowness of movement, stiffness, a loss of automatic movements such as blinking and smiling, changes in speech and, in the later stages of the disease, dementia.
Investigating whether SNCA genetic variation relates to pathological variation in Parkinson’s disease
Mutations in the SNCA gene (encoding alpha-synuclein) cause autosomal dominant forms of Parkinson’s disease. This project aims to determine whether generic variation in SNCA relates to pathological severity of inclusion pathologies and alpha-synuclein protein levels.
With Dr Scott Kim (SRO)
The major focus of these projects is to understand the role of lipid dysfunction in Parkinson’s disease and the related disorder of multiple system atrophy. Increasing evidence shows that lipids regulate a number of neurodegenerative processes.
Understanding the role of lipids in alpha-synuclein aggregation process in parkinsonian syndromes
We have recently produced compelling evidence showing that lipid levels are significantly altered in disease-affected regions of parkinsonian syndromes. This project aims is to determine how lipids regulate alpha-synuclein aggregation process in parkinsonian syndromes.
Determining the role of COQ2 in multiple system atrophy pathogenesis
Myelin is a specialised lipid membrane that encases the axons of all neurons in the brain and is made by oligodendrocytes. These cells do not properly make myelin and degenerate in certain brain regions in multiple system atrophy. Without myelin neurons eventually die. Genome-wide association studies indicate that COQ2 is associated with an increased risk for multiple system atrophy. The aim of this project is to determine the role of COQ2 in the pathogenesis of multiple system atrophy.
With Dr Nicolas Dzamko (RO)
The major focus of these projects is to understand how mutations in certain genes cause inherited forms of Parkinson’s disease and whether/how these genes also contribute to non-inherited (sporadic) Parkinson’s disease. A particular focus is on leucine-rich repeat kinase 2 (LRRK2), a promising therapeutic target for Parkinson’s disease.
Measuring LRRK2 by flow cytometry
The LRRK2 protein is highly expressed in white blood cells. The aim of this project is to establish a flow cytometry assay to measure LRRK2 protein in white blood cells from Parkinson’s disease patients. This assay could then be used to monitor LRRK2 in any clinical trials using drugs to block LRRK2 function.
Effect of LRRK2 mutations on PD-associated inflammation
Inflammation is a common feature of Parkinson’s disease and LRRK2 is involved in the regulation of inflammation. This project aims to measure inflammatory markers in the serum and cerebrospinal fluid of subjects that have LRRK2 mutations but not yet Parkinson’s disease. We will determine if inflammation occurs early in the disease process and whether certain inflammatory markers can be used to predict Parkinson’s disease before clinical symptoms.
LRRK2 expression in brain
LRRK2 is promising drug target for the treatment of Parkinson’s disease. This projects aims to understand what happens to LRRK2 in the brain of Parkinson’s patients. This information will aid drug development and clinical trials for LRRK2 inhibitors.
LRRK2 and idiopathic Parkinson’s disease
Pathogenic mutations in LRRK2 cause inherited Parkinson’s disease but polymorphisms in LRRK2 are also a risk factor for sporadic Parkinson’s disease. This project aims to measure LRRK2 protein and its function in sporadic Parkinson’s disease patients. Results from this work will help determine if LRRK2 blocking drugs will be beneficial for all forms of Parkinson’s disease.
LRRK2 and type-1 interferon
We have established that LRRK2 is involved in inflammatory pathways that regulate interferon production. This project will generate and utilise state-of-the-art cellular models (induced pluripotent stems cells and crispr/cas9 genome editing) to understand how Parkinson’s disease-causing LRRK2 mutations affect inflammation.
TLR2 and the pathological spread of alpha-synuclein
The accumulation of insoluble alpha-synuclein protein is a hallmark feature of brain tissue from Parkinson’s patients. Recent evidence suggests that alpha-synuclein may spread through the brain in a prion-like manner, contributing to neurodegeneration. This project aims to determine the contribution that the toll-like receptor 2 (TLR2) makes to the spread of alpha-synuclein through the brain.
The association of VPS35 and pathological alpha-synuclein
Mutations in VPS35 are a rare cause of inherited Parkinson’s disease. Recent evidence suggests that VPS35 mutations may contribute to the accumulation of alpha-synuclein protein. This project aims to determine the association between VPS35 and alpha-synuclein in human Parkinson’s disease brain and to use cellular models to define this relationship.
Implications of neuronal toll-like receptor activation for Parkinson’s disease
Neuroinflammation contributes to cell death in Parkinson’s disease but how and via which pathways is mostly unknown. This project uses cell models to determine the contribution of the major inflammatory regulating toll-like receptor (TLR) pathway to neuroinflammation, with a particular focus on the largely unexplored role of TLR signalling in neurons.
Both GSK3B and MAPT genes control crucial processes in the cell. We have shown that genetic polymorphisms in these two genes interact to increase risk for late-onset, idiopathic neurodegeneration. We aim to discover whether the two genes will have an effect in other diseases and to determine the biological mechanisms in the genes act to increase disease risk.
I invite you to read our latest publication – NeuRA’s 2016 Profile – where we have divided our research into five sections: childhood, adolescence, adulthood, midlife and older age to reflect the considerable range and diversity of our research. Significant achievements in human progress have come from harnessing the power of medical research, technology and innovation to accelerate health interventions. […]