Mutations in the PARK-1 and PARK-4 genes leads to alpha-synuclein aggregation with pathology eventually resembling that of sporadic PD. One question is whether the insoluble form of alpha-synuclein is the cause for neurodegeneration or, alternatively, alpha-synuclein in the form of oligomers is the true toxic species. Dr. Jensen hypothesizes that it the latter form of alpha-synuclein that is the culprit for neurodegeneration. Furthermore, in identifying possible targets for these oligomers of alpha-synuclein, Dr. Jensen may be able to highlight novel disease pathways. In this way, he hopes to facilitate the development of PD models and ultimately identify new targets for neuroprotective therapies.
Final Outcome
Dr. Jensen successfully identified multiple oligomer-specific targets. He is now conducting a quantitative comparative analysis of brain proteins associated to alpha-synuclein to better identify those to validate for oligomer binding ability. The results of the MJFF project now form the basis for Dr. Jensen's participation in an academic-industrial training network on alpha-synuclein-related brain diseases funded by the European Union.