Synaptic Protein-Protein Interaction Networks unravel insights into Parkinson's Disease

Research output: Contribution to conferencePoster

Abstract / Description of output

Parkinson’s Disease (PD) is the second most common neurodegenerative disease in the
Western World. Dysfunction and subsequent degeneration of dopaminergic neurons leads to classic symptoms featuring disorders in motor function followed by other non-motor symptoms including depression and cognitive decline. However the disease is complex. Modern high-throughput analysis in recent years has identified affected pathways and proteins including mitochondrial dysfunction, abnormalities in the ubiquitin pathway and disrupted vesicle transport.
Synaptic dysfunction is one of the models for the early stages of the disease and hence we looked at how these datasets relate to the molecular complexes found at the human
synapse. Proteomic and protein-protein interaction datasets were used to generate
molecular maps of the synapse. We extracted evidence for proteins and genes associated with PD from a variety of sources including GWAS studies, databases and literature. We found that the synaptic datasets were significantly enriched with subset of PD-related proteins. In order to identify structural clusters within the network we used a spectral community algorithm. We then overlaid genetic association data and molecular function annotations from the Gene Ontology (GO). Hypergeometric testing was used to detect enrichment of molecular clusters for both disease and functional class associations. We have identified clear molecular clusters within both pre- and post synapses that were specifically enriched in proteins linked to Parkinson’s Disease. In addition, in the presynapse, significant enrichment for GO terms related to synaptic vesicle cycling is associated with PD enriched clusters. In summary our analysis reveals that despite the complex nature of integrating disease associations from many sources, when applied onto a molecular model of the synapse specific substructures and mechanisms clearly emerge.
Original languageEnglish
Publication statusPublished - 16 Sept 2016
EventInternational Conference on Systems Biology - Barcelona Palau de Congressos, Barcelona, Spain
Duration: 16 Sept 201621 Sept 2016


ConferenceInternational Conference on Systems Biology
Abbreviated titleICSB 2016
Internet address


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