Roberta Marongiu, PhD Research & Impact Research Investigators Roberta Marongiu, PhD Investigator: Roberta Marongiu, PhD Name of Institution: Weill Cornell Medicine, New York, NY Project Title: Menopause as an important transition state in the susceptibility to Parkinson’s disease (PD) Investigator Bio: Dr. Marongiu obtained her PhD in Neurogenetics and Neuroscience from the Sapienza University of Rome, Italy, and the University of California San Diego, where she studied the Pink1 gene responsible for an inherited form of Parkinsonism. After having worked with Dr. Eliezer Masliah at UCSD, she trained as postdoctoral fellow with Dr. Michael Kaplitt at Weill Cornell Medical College with research focused on the identification of molecular targets for gene therapy approaches for PD. She joined the Weill Cornell Medicine faculty in 2016 as Assistant Professor of Neuroscience Research in the Department of Neurological Surgery, with an appointment at the Brain and Mind Research Institute, where she continues her gene therapy studies for motor and non-motor symptoms of PD. Specifically, her research interests lie in understanding the brain mechanisms that influence the differences in onset and course of PD in men and women. Objective: The goal is to characterize the influence of the estrogen decline during menopause on susceptibility to PD in a mouse model overexpressing alpha-synuclein (αsyn). Background: Pre-menopausal women have about a 2-fold reduced risk of developing PD as compared to men and post-menopausal women, suggesting that estrogen plays an important role in protecting against PD. Early menopause, either natural or surgical, is associated with an increased risk of PD. Menopausal women who had received estrogen are less likely to develop PD than those who had not. However, the mechanisms underlying the protective role of estrogen against PD progression remain unclear. We hypothesize that loss of estrogen during menopause will decrease the neuroprotective advantage observed in young female mice, accelerating the appearance and progression of PD in our mouse model. Methods/Design: We will use a mouse model of PD which was engineered to contain human αsyn and which demonstrates αsyn pathology in the brain, resultant nerve degeneration, and motor impairment. In this model, we will characterize the influence of inducing menopause on PD pathology and motor deficits. Relevance to Diagnosis/Treatment of Parkinson’s disease: The proposed work will help to clarify the ways in which estrogen influences PD progression. A better understanding of the underlying molecular mechanisms can lead to the development of novel targeted treatments for PD.