Mar 04, 2014
from 04:30 PM to 05:30 PM
|Where||Keynes Hall in King's College|
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Title: "Network Pharmacology for Parkinson's Disease"
Network pharmacology offers a new approach to identifying potential drug targets in diseases with complex aetiology. Parkinson’s disease (PD) is used as an exemplar of such a disease due to its sporadic nature and the involvement of multiple cellular pathways. PD is the second most common neurodegenerative disease with a prevalence of 5% at age 85. Despite this, there is currently no cure for PD or treatment capable of slowing disease progression. Many of the key features of PD can be reproduced using the neurotoxin MPP+, a complex I inhibitor that induces cytotoxicity via a programmed cell death (apoptotic) mechanism. Although key processes in MPP+ toxicity have been characterised, analysis of the underlying biological network can offer an insight into the interplay of these individual processes and pathways.
I will discuss the construction of protein-protein interaction networks (PPN) to model MPP+ induced cell death, using iRefIndex as a consolidated source of protein-protein interaction data. I analysed these networks to identify nodes whose deletion was expected to have a significant effect on MPP+ induced cell death and validated these predictions using our in vitro system. I further demonstrated that a partial rescue from MPP+ neurotoxicity can be achieved using the combined overexpression of four network targets. However, no single intervention is effective: we need multiple, targeted interventions to alter the biological outcome of the system. As well as the biological insights into the MPP+ model of PD, this was an exciting opportunity to directly test the approach of network pharmacology in vitro, and I will discuss the opportunities and challenges presented.