Identification of new components in Parkinson's Disease signalling pathways

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Our knowledge of the molecular events leading to Parkinson‘s disease (PD) is being greatly enhanced by the study of familial forms of the disease. Professor Wood‘s laboratory has identified a gene (PINK1) which when mutated causes nerve cell death and ultimately PD. Moreover, point mutations in a second gene called HtrA2 have also recently been identified as a susceptibility factor for PD. One of the first questions which arise is; do these two molecules interact either together or in the same pathway or process to produce PD? We have very recently established that they not only interact in the same pathway but that PINK1 regulates the activity of HtrA2. However much more work needs to be done to understand these processes more fully. This application focuses on this pathway and uses a range of molecular biological and cellular techniques to identify other proteins involved in this process. We plan to assess how these proteins talk to each other and how important this crosstalk is in the development of the disease. To this end we have already developed the core resources of appropriate cell models and have identified human brain tissue carrying abnormalities in the PINK1 gene. Moreover, we will have access to mice and flies in which HtrA2 and PINK1 genes have been disrupted.If we can indeed discover more of the pathway to cell dysfunction and death, then this in turn provides more options for therapeutic intervention.