One of the main hurdles limiting widespread application of gene therapy in humans is the inability to target production of therapeutic protein to only specific cells affected in the disease process. We have designed a novel gene regulation system that can sense cell stress to switch on and restrict expression of a therapeutic gene in only those cells at risk. The objective of this proposal is to test the functionality of our gene regulation system in regulating parkin and mir7/mirRNA-syn, representative of two classes of therapeutic molecules for Parkinson's disease. We will determine whether our gene regulation system can control these neuroprotective molecules at a sufficient level in stressed cells to prevent neuronal cell death and motor deficits in animal models of Parkinson's disease. The outcomes of this research address an unmet need for methods of physiological regulation of therapeutic genes and will have major implications for human gene therapy.