Funded Studies
Objective/Rationale:
Mitochondria are the powerplants of the cell, and decades of evidence suggest that they may be defective in the brains of people with Parkinson’s. The overall goal of this project is to determine whether the protein ‘Ndufaf2’ can be used to improve mitochondrial function in a way uniquely relevant to Parkinson’s disease. Here, we will examine the ability of Ndufaf2 to improve mitochondrial function and prevent neuronal cell death in models of Parkinson’s disease.
Project Description:
Our preliminary data show that a protein called ‘Ndufaf2’ can improve the function of a key enzyme within mitochondria. We will use gene-delivery techniques to increase Ndufaf2 in pre-clinical models and confirm improved mitochondrial function in the intact brain. Next we will determine whether modulation of Ndufaf2 can rescue the mitochondrial deficits in a model of familial Parkinson’s disease and/or prevent cell death in a model of Parkinson’s disease-like neurodegeneration.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Dysfunction of mitochondria has been implicated as a cause of both familial and sporadic forms of Parkinson’s disease. The goal of this project is to test the idea that Ndufaf2 may counteract what are thought to be some of the underlying causes of Parkinson’s disease, potentially identifying Ndufaf2 as therapeutic target for disease intervention.
Anticipated Outcome:
Through the completion of this project, we will understand whether upregulation of the mitochondrial chaperone Ndufaf2 possesses therapeutic benefits in two distinct models of Parkinson’s disease. If successful, future efforts would be designed around identifying small molecules that can mimic Ndufa2 function, or those that induce its expression in the brain, to rescue brain cells that are otherwise vulnerable in Parkinson’s disease.