Disease mechanisms
Neurological disease
Alzheimer's disease
Alzheimer's disease is the most common form of dementia; a term used to describe various different brain disorders that have in common a loss of brain function that is usually progressive and eventually severe. There are over 100 different types of dementia - the most common are Alzheimer's disease, vascular dementia and dementia with Lewy bodies. The Alzheimer's Society estimates that there are currently over 750,000 people in the UK who suffer from some form of dementia, with over half diagnosed with Alzheimer's disease.
Studies within the BMRC are focused on cellular events that lead to the development of Alzheimer's disease by investigating the post-translational processing of APP in normal and stressed cells.
Research in this area is led by Professor David Parkinson.
Epilepsy
Temporal lobe epilepsy (TLE) is one of the most prominent forms of epilepsy in adults and is associated with hippocampal sclerosis. It is accompanied by a range of symptoms including: temporary confusion, staring spells and uncontrollable jerking movements of the arms and legs. Unfortunately epilepsy still represents a 'stigma' and if not treated properly it disrupts daily life routine. Some of the patients affected do not respond to drug treatments, despite a large number of studies having been conducted to understand the reason for this. Thus there is still a great need for further research into the causes and pathogenesis of epilepsy.
Research in this area is led by Dr Alessandra Princivalle.
Multiple Sclerosis
Multiple Sclerosis (MS) is the most common disabling neurological condition among young adults, affecting around 85,000 people in the UK alone. MS is an autoimmune disorder which arises as result of the body's own immune system attacking the myelin sheath, a protective lipid rich membrane that surrounds the nerve fibres of the central nervous system. Damage to myelin interferes with the progress of messages between the brain and other parts of the body causing the symptoms associated with MS.
Research in the BMRC has a particular focus on the role of chemokines and the metalloproteinase family of enzymes in disease pathogenesis, in particular the enzyme ADAM17. Post-translational modification of arginine residues in a process called citrullination is also being assessed in the CNS in people with MS and in conjunction with neurology consultants at the Sheffield Teaching Hospitals NHS Foundation Trust we ae investigating the role this may play in autoantibody production in MS. It is hoped that this research will lead to the development of new therapeutics targeting inflammatory mediators.
Studies are led by Professor Nicola Woodroofe and Dr Rowena Bunning.
Muscular Dystrophy
There are about 60 different types of muscular dystrophy and related neuromuscular conditions, all are characterised by progressive muscle wasting or nerve deterioration, which can cause a loss of muscle strength and shortened life expectancy. The great majority are inherited conditions and have a genetic basis. Although there are presently no cures, gene therapy and cell therapy trials, for Duchenne muscular dystrophy in particular, have been carried out.
Research within the BMRC focuses on Duchenne and myotonic dystrophies (the latter associated with DNA expansions in the defective genotype). By examining gene expression patterns, it is hoped to develop an understanding of the biochemical and cellular bases underlying the diverse genetic phenotypes.
Studies in this area are led by Professor Peter Strong.
Schizophrenia
Schizophrenia is a severe brain disease that interferes with normal brain and mental function, which can trigger a range of symptoms including: hallucinations, delusions and paranoia. Without treatment the condition affects the sufferer's ability to think clearly, manage emotions and interact socially. Although there are a number of theories the exact cause of the disease has not been determines and continues to be the focus of much research.
Studies within the BMRC are led by Dr Caroline Dalton in collaboration with Professor Gavin Reynolds.
Parkinson's disease (PD)
PD occurs in 0.17 per cent of the general population affecting ~1 to 2 per cent of those over 80 years old. Although rare heritable forms of PD have been documented, the sporadic form is far more common and this is possibly connected to environmental factors. The molecular mechanisms of neurodegeneration in PD are mostly unknown and the lack of preventative treatments for PD is undoubtedly a result of our limited understanding of the underlying aetiology. A critical step is the formation of Lewy bodies, in which alpha-synuclein in the form of amyloid-like aggregates has been identified as a major component. Soluble alpha-synuclein oligomers populated during amyloid assembly have been implicated as the causative agent in PD.
Research within the BMRC is focused on linking the structural properties of amyloid oligomers thought to be responsible for cell death to their toxic mechanism. Ion-mobility-spectrometry mass-spectrometry is used to characterise the size and shape of these oligomeric species.
Studies within the BMRC are led by Dr David Smith
