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Target Validation Studies for the Discovery of Novel Small Molecule Therapeutics with the Potential to Modify Disease Outcome by Inhibiting Bacterial Amyloid Protein-induced Alpha-synuclein Aggregation and Associated Neuronal Toxicity
… death of nerves within the gut (i.e., the enteric nervous system), driven by accumulation of toxic forms of the … symptoms. This program seeks to develop a new experimental system that accurately replicates Parkinson’s disease biology in enteric nervous system cell cultures. The investigators will use it to …
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Pharmacological Targeting of the 5-HT1, A2A and NMDA Receptors: An Integrative Approach to Dyskinesia
… Objective/Rationale: The glutamate, serotonin and adenosine systems are interesting targets for pharmacological … disease. However, interventions addressed at single systems have so far produced limited results. Indeed, the … are complex and affect the function of several brain systems. In this project we intend to counteract dyskinesia …
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Evaluating the Role of Natural Killer Cells in Parkinson's Pathology
… killer (NK) cells play a protective role on the nervous system in Parkinson’s disease. We evaluated the role of NK … cells in synuclein-related diseases that affect the nervous system. Our study provided evidence of potential usefulness … demonstrated the protective role of NK cells on the nervous system in a preclinical model of Parkinson’s. The next steps …
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LRRK2 GTPase Validation and Inhibitor Discovery
… GTPase activation in vitro. Final Outcome After testing multiple sources of LRRK2, we found that only LRRK2 isolated … a robust assay for GDP production by LRRK2. We identified multiple hit compounds that reproducibly inhibited GDP …
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Multiphosphatase Inhibitors as PD Therapeutics
… Objective/Rationale: Parkinson’s disease has multiple genetic and environmental causes. As a result, … or pharmacological tools was found to be protective in multiple animal models of Parkinson’s disease, stroke, …
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Development of Disease Modifying Therapeutic for Parkinson's Disease
… target for PD research. LRRK-2 is a large protein with multiple functional domains, including a protein kinase … has well-recognized expertise in this approach, having multiple ongoing kinase inhibitor programs in several …