Parkin is a protein made by all cells in the body, including brain cells. It plays an important role in the protection of neurons through a process known as quality control. Changes (mutations) in parkin that impair its function are known to cause early-onset parkinsonism, an inherited form of Parkinson's disease (PD). Restoring the function of parkin could slow or even stop the progression of all types of PD.
We hypothesize that the activation of parkin with small-molecule drugs could treat PD.
First, using computational methods, we will determine which regions (parts) of parkin are responsible for its activation. After the selection of the region most likely to activate parkin, a combination of mathematical and experimental methods will be used to identify small molecules that may bind to this promising region. The search for such molecules will take advantage of a new technology that empowers researchers with artificial intelligence to maximize the success of finding small-molecule activators of parkin.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The small molecules identified in this study may be used to design new drugs for PD. As no existing or prospective drug modifies the activity of parkin, a new class of therapeutics could be developed. Additionally, such therapeutics could be useful in studying the role of parkin activation in Parkinson's disease.
Next Steps for Development:
The identified small molecules that activate parkin should serve as a starting point for drug discovery and development. This would allow the small molecules to be further optimized by improving their pharmacological properties and ability to activate parkin.