Defining Structural Forms of Alpha-synuclein Responsible for Key Features Associated with Parkinson's Disease

Study Rationale:
The alpha-synuclein pre-formed fibril (PFF) model shows promise for modeling many features of Parkinson’s disease (PD). In this model, PFFs induce pathological features and behaviors that closely resemble those found in PD. The PFFs consist of a mixture of different structural forms of alpha-synuclein and it is not known which form is responsible for PD.

Hypothesis:
We will develop standard operating procedures to produce defined structural forms of alpha-synuclein that can be standardized in pre-clinical PD models for reliable phenotypes (features of the disease).

Study Design:
Different forms of alpha-synuclein will be generated and characterized using biophysical methods. The effects of each form of alpha-synuclein on pathologic features and behaviors related to PD will be evaluated.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
This study will help to standardize the PFF model to reliably reproduce key features associated with PD. This model can be used to validate findings from human studies related to therapeutics, biomarkers, genetics and epidemiology. In addition, this model can help identify novel therapeutic targets.

Next Steps for Development:
Therapeutic strategies that specifically target each distinct alpha-synuclein species may be developed based on the findings of this study.