Neurological: A broad-based approach to monitoring neurological disease genes in vivo.

Lead researchers: Professor Alex Wade, Department of Psychology, and Dr Chris Elliott, Department of Biology

Professor Alex Wade and Dr Chris Elliott are combining basic research in invertebrate (Drosophila) animal models with human patient studies to elucidate the way in which Parkinson’s disease (PD) affects neuronal signalling in the central nervous system. They have focused on visual transduction as a model system that is accessible in all models.

Wade and Elliott find that PD significantly alters visual processing in all the organisms they examined. In flies they saw an overall effect of increased neuronal function in younger organisms – consistent with a model of PD-related excitoxicity (Himmelberg, West, Wade, & Elliott, 2018). In collaboration with an industrial partner, they have shown that a kinase inhibitor tool compound (BMPBB32) is able to normalise visual responses in Drosophila carrying a specific kinase-dependent PD gene (LRRK2-G2019S) (Afsari et al., 2014).

The team has also trialled the use of machine learning algorithms to classify phenotype and genotype in flies, rats and humans based on multidimensional data from visually-evoked steady-state electrophysiology. Again, in all organisms (including humans) both the presence and type of PD genes can be classified based solely on rapid electrophysiological assessments of the visual system (Himmelberg, West, Elliott, & Wade, 2018; West, Elliott, & Wade, 2015). The findings have significant implications for the detection, monitoring and treatment of this neurodegenerative disease.

References

1. Afsari, F., Christensen, K. V., Smith, G. P., Hentzer, M., Nippe, O. M., Elliott, C. J. H., & Wade, A. R. (2014). Abnormal visual gain control in a Parkinson’s disease model. Human Molecular Genetics, 23(17), 4465–4478. https://doi.org/10.1093/hmg/ddu159
2. Himmelberg, M. M., West, R. J. H., Elliott, C. J. H., & Wade, A. R. (2018). Abnormal visual gain control and excitotoxicity in early-onset Parkinson’s disease Drosophila models. Journal of Neurophysiology, 119(3), 957–970. https://doi.org/10.1152/jn.00681.2017
3. Himmelberg, M. M., West, R. J. H., Wade, A. R., & Elliott, C. J. H. (2018). A perceptive plus in Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 33(2), 248. https://doi.org/10.1002/mds.27240
4. West, R. J. H., Elliott, C. J. H., & Wade, A. R. (2015). Classification of Parkinson’s Disease Genotypes in Drosophila Using Spatiotemporal Profiling of Vision. Scientific Reports, 5. https://doi.org/10.1038/srep16933