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Searching for Cellular Changes Associated with PINK1 and PRKN Mutations

Study Rationale:
PINK1 and parkin are two proteins that work together to keep cells healthy by ridding them of damaged mitochondria, cells' powerhouses. Mutations (changes) in the PINK1 and PRKN genes are linked to inherited early-onset Parkinson's disease (PD). Under conditions that wreak havoc on mitochondria, PINK1 and PRKN mutations play a role in cell response to the damage. In the healthy cell, however, the role of these mutations is unclear. To clarify their role under normal conditions, we will study a uniquely large collection of fibroblasts -- cells from the skin -- from individuals with PINK1 and PRKN mutations.

To find a specific PINK1/PRKN signature -- one or more cellular change associated with PINK1 and PRKN mutations -- we will compare protein production (gene expression) and breakdown (metabolism) in cells with PINK1 and PRKN mutations to those in cells without mutations in these genes.

Study Design:
We will analyze gene expression and metabolism in skin cells with PINK1 and/or PRKN mutations. We expect challenges with interpreting our findings and plan to use two experimental approaches -- cells from biologically related individuals and immature brain cells with changes in PINK1 and PRKN genes -- to make sense of data collected. We will then analyze genetic and metabolic changes in the cells separately and identify links between the two.

Impact on Diagnosis/Treatment of Parkinson's disease:
Identifying a PINK1/PRKN signature is a very important step in the search for biomarkers -- objective measures of disease -- useful in diagnostics. This signature would also aid in selection of clinical research participants.

Next Steps for Development:
The identified signature will be tested in individuals with PD without mutations in PINK1 or PRKN genes and in those whose disease is not inherited. Testing the occurrence of the signature in other cells of individuals with Parkinson's, such as blood cells, will also be important in the future.


  • Fabienne C. Fiesel, PhD

    Jacksonville, FL United States

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