Molecular Pathogenesis of Neurodegenerative Diseases
Alzheimer's Disease, dementia, protein aggregation, animal model
My group is dedicated to discovering the molecular pathogenesis of neurodegenerative diseases using the fruit fly, Drosophila melanogaster, as our primary tool. Our creation of a fly model of Alzheimer's disease by expressing the amyloid beta peptide in the insect's brain has started two interlinked lines of research. The first uses the powerful genetic tools that are available in the fly to find genes that modify the brain's sensitivity to the toxic effects of the Ab peptide. Genetic screens have revealed important pathways of disease that we are investigating using biochemical, cell culture and animal modelling approaches. The second strand, in collaboration with Prof. Chris Dobson and Dr. Michele Vendruscolo in the Dept. of Chemistry, correlates the biophysical properties of peptides with their aggregation propensity. The fly allows us to observe the generic toxicity of protein aggregates in vivo.
Image at top of page: Brain section from Alzheimer’s fly showing actin in green, nuclei in blue, and amyloid beta plaque in red.
4 key publications
- Moloney, A., Sattelle, D.B., Lomas, D.A., and Crowther, D.C., Alzheimer's disease: insights from Drosophila melanogaster models. Trends Biochem Sci (2009) epub Dec 2009
- Rival, T., Page, R.M., Chandraratna, D.S., Sendall, T.J., Ryder, E., Liu, B., Lewis, H., Rosahl, T., Hider, R., Camargo, L.M., Shearman, M.S., Crowther, D.C., and Lomas, D.A. (2009) Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer's disease. Eur J Neurosci 29, 1335-1347
- Nerelius, C., Sandegren, A., Sargsyan, H., Raunak, R., Leijonmarck, H., Chatterjee, U., Fisahn, A., Imarisio, S., Lomas, D.A., Crowther, D.C., Stromberg, R., and Johansson, J. (2009) Alpha-helix targeting reduces amyloid-beta peptide toxicity. Proc Natl Acad Sci U S A 106, 9191-9196
- Luheshi, L.M., Tartaglia, G.G., Brorsson, A.C., Pawar, A.P., Watson, I.E., Chiti, F., Vendruscolo, M., Lomas, D.A., Dobson, C.M., and Crowther, D.C. (2007) Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid beta Pathogenicity. PLoS Biol 5, e290