Parkinson’s disease is characterized by the misfolding and accumulation of the alpha-synuclein protein in the brain. Therefore, alpha-synuclein-based disease models are used for studying disease mechanisms and developing new therapies. Most of these models and studies of pathological alpha-synuclein use misfolded protein artificially generated in test tubes. However, its properties could be very different from misfolded alpha-synuclein in brain tissue of people with Parkinson’s. To better understand disease and to develop better disease models, it is critical to analyze the properties of misfolded alpha-synuclein in Parkinson’s brains. However, this is challenging because misfolded alpha-synuclein isolated from patients is very impure and low in amount.
The goal of the proposed study is to solve these technical challenges and to systematically analyze the properties of misfolded alpha-synuclein in Parkinson’s patients.
We propose to develop new techniques to isolate highly purified misfolded alpha-synuclein from patients and to systematically study the properties of misfolded alpha-synuclein in Parkinson’s brains using multiple models. Moreover, we also propose to establish a protocol to amplify these misfolded alpha-synuclein from patients.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This detailed analysis will dramatically improve our understanding of the etiology of Parkinson’s and facilitate the discovery of new drug targets. The development of new technology to amplify pathological alpha-synuclein in Parkinson’s brains will enable us to establish better models for drug discovery and therapeutic development and will also make this critical resource available to many labs around the world, which will dramatically facilitate the study of Parkinson’s disease.
Next Steps for Development:
After the successful establishment of these new technologies, we use these new models to explore new disease mechanisms. Moreover, we will also share these precious materials with researchers in academia and industry to facilitate the development of therapies against Parkinson’s disease.