Dysfunction of mitochondria, the powerhouses of the cell, has been linked to degeneration in nerve cells in Parkinson’s disease. When mitochondria can’t function properly, cellular energy levels are depleted and damaging molecules are released, contributing to nerve cell death. Mitochondrial quality control, getting rid of bad mitochondria, is therefore critically important. Here, we aim to identify compounds that improve the recognition and removal of damaged mitochondria from the cell.
We aim to identify novel compounds that improve the recognition and clearance of defective mitochondria, limiting nerve cell degeneration and slowing or stopping the progression of Parkinson’s disease.
During the first half of the project, we will use cells from a person with Parkinson’s disease who has partial loss-of-function mutation in the mitochondrial quality control pathway. Using these cells, we will assess the activity of molecules within our collection, encompassing over 100,000 compounds, to identify those that improve the recognition of damaged mitochondria. During the second half of the project, we will test our successful compounds in multiple biology assays and use modern genetic and analytical techniques to identify how the compounds are working.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The compounds identified and the mechanisms by which they are working, will firstly give insight into novel biological regulators of the disease, identifying targets for future drug discovery and provide starting material that could developed into Parkinson’s disease therapy.
Next Steps for Development:
Should we be successful, the compounds identified in this study will be used as a starting point for further efforts to synthesize better compounds, with optimized properties, that are safe and amenable to testing in other models of Parkinson’s disease.