Constanza J. Cortes, PhD APDA Research & Impact Research Investigators Constanza J. Cortes, PhD Investigator: Constanza J. Cortes, PhD Name of Institution: University of Alabama at Birmingham, Birmingham, AL Project Title: Exercise-Mimetics: novel neuroprotectant pathways in Parkinson disease Investigator Bio: Dr. Cortes is an Assistant Professor in the Department of Cell, Developmental, and Integrative Biology at the University of Alabama at Birmingham. She obtained her PhD from the University of Chicago focusing on autophagy mechanisms underlying the pathogenesis of genetic prion disorders. She did her postdoc at the University of California San Diego, working on the role of autophagy dysfunction in polyglutamine disease. After a short tenure at Duke University as research faculty, she has had her own lab since October 2019 at UAB. Her group studies brain aging, especially in the context of physiology and neuropathology, and investigates exercise as an intervention for age-associated neurodegenerative diseases. Objective: To understand the molecular underpinnings of the neuroprotective effects of exercise. Background: Physical activity has extensive and well-documented neuroprotective effects, benefitting cognitive function during healthy aging and reducing the risk of age-associated neurodegenerative disorders, including Parkinson’s disease (PD). Epidemiological data suggests that aerobic exercise may reduce the risk of PD development, and pre-clinical studies demonstrate that exercise upregulates neurotrophic factors in the substantia nigra and can protect against neurotoxicity. The mechanisms responsible for the brain benefits of exercise, however, remain largely unexplored. Interestingly, the benefits of exercise have been shown to be transferable between individuals via plasma transfer, suggesting that circulating factors in the blood may be responsible. Identification of the secreted signals that underlie the benefits of exercise can help to identify potential neuroprotective agents in PD. Methods/Design: In this project, we test the hypothesis that exercise can reduce PD-associated pathology in the brain, using behavioral exercise interventions in mice. We will also introduce PD pathology into our unique transgenic mice that are engineered to display similar neuroprotective effects despite living a sedentary lifestyle. We will determine if our mice can withstand PD pathology more than wild type mice. In parallel, we will also determine if aging is a contributing factor to PD-associated toxicity in the brain, by examining established pathological findings of the pre-formed fibril alpha-synuclein model in the aging brain. Relevance to Diagnosis/Treatment of Parkinson’s disease: Our studies into the neuroprotective effects of exercise will help to define therapies that harness these effects to benefit people with PD.