This grant builds upon the research from a prior grant: Evaluation of the Parkin Pathway to Study Neural Mitophagy
Promising Outcomes of Original Grant:
Mitophagy is a cellular process during which damaged mitochondria, or energy generators, are broken down. Mitophagy has been suspected to malfunction in Parkinson's disease (PD), but evidence to support this does not exist. Using our new pre-clinical model, we have proven that mitophagy does take place in healthy brain cells but does not require a series of chemical reactions within the cell that involve PINK1 and Parkin proteins to be active. In contrast, this pathway is active in early-onset PD, but does not function as it should. We now aim to determine whether mitophagy indeed malfunctions in the brains of individuals with Parkinson's, and if so, whether that causes the disease.
Objectives for Supplemental Investigation:
We have demonstrated that mitophagy does take place in the brains of healthy pre-clinical models, so our next step is to study mitophagy in the brains of pre-clinical models with Parkinson's symptoms. We will induce these symptoms using a combination of genetic and pharmacological methods. The three main objectives of this study are 1) to determine whether mitophagy takes place within distinct areas of the brain; 2) to establish whether PINK1/Parkin pathway is active; and 3) to determine whether mitophagy, if induced, requires the PINK1/Parkin pathway to be active in pre-clinical models of Parkinson's.
Importance of This Research for the Development of a New PD Therapy:
This work can confirm whether mitophagy malfunctions in the brain of individuals with Parkinson's. If it does, developing therapies to target mitophagy will provide a therapeutic target.