Molecular mechanisms that underlie
neurodegenerative disease
We are using genetic and genomic approaches in model organisms to unravel the molecular mechanisms involved in the pathology of neurodegenerative disorders, such as Huntington's Disease (HD) and Parkinson's Disease (PD).Huntington's disease (HD) is a fatal neurodegenerative disorder inherited in an autosomal dominant manner. This disease is caused by an expansion of a polyglutamine tract in the protein Huntington (Htt) and is characterised by atrophy in the striatum and cortex of the brain. Although the initiating trigger in HD is known, the critical molecular mechanisms underlying this devastating illness remain unresolved. Our work focuses on elucidating these molecular mechanisms with the hope of aiding in the development of therapeutic strategies for HD.
Parkinson's disease (PD) is the second most common neurodegenerative disorder in the Western world after Alzheimer’s disease and is characterized by dopaminergic cell loss in the substantia nigra and the presence of cytoplasmic proteinaceous inclusions called Lewy bodies.. Depletion of dopamine in the striatum causes deregulation of the motor circuits that project throughout the basal ganglia, resulting in the clinical manifestations of PD (resting tremor, slowness of movement, muscular rigidity, and postural instability). The percentage of affected individuals is ~1-2% at 65 years and raises to ~5% at 85 years. The vast majority of PD cases are thought to be idiopathic but 5-10% are due to a genetic component, showing both dominant and recessive modes of inheritance. Linkage data has identified ten loci, named PARK, and mutations in several genes have already been mapped. Our work, in collaboration with Dr Tiago Outeiro (IMM, Lisbon), is focused on DJ-1 (PARK7).We are using yeast models of HD and PD to characterise conserved mechanisms involved in pathology of these diseases and to perform genetic screens to identify additional genes that modify disease-relevant phenotypes. In addition, we are validating these genetic modifiers of HD and PD in several model systems, including Drosophila and mammalian cells.
Department of Genetics
University of Leicester
University Road, Adrian building
Leicester LE1 7RH , U.K.
Tel: +44 (0)116 252 3485
Fax: +44 (0)116 252 3378
E-Mail: fg36@le.ac.uk
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