Investigator:
Naemeh Pourshafie, PhD
Name of Institution:
University of Pennsylvania, Philadelphia, PA
Project Title:
Enhancing neuronal resilience to neurodegeneration via the epigenetic-metabolic axis
Investigator Bio:
Dr. Pourshafie is a post-doctoral fellow at the Epigenetics Institute in the Perlman School of Medicine at the University of Pennsylvania. In 2020, Dr. Pourshafie completed her PhD as part of the George Washington University-National Institute of Health (NIH) Partnership Program. During her doctoral studies, she worked in the laboratory of Dr. Kenneth Fischbeck at the National Institute of Neurological Disorders (NINDS/NIH).
Dr. Pourshafie is currently working under the guidance of Dr. Shelley Berger and Dr. Nancy Bonini with a primary focus on memory-related neurodegenerative disorders, particularly Parkinson’s disease (PD), Alzheimer’s disease (AD), and related dementias. Her research efforts are focused on investigating the role of epigenetics and metabolism in disease-related dementia. She is studying a metabolic protein that regulates gene expression, aiming to uncover its potential as a therapeutic agent.
Objective:
This project aims to unravel the intricate relationship between two proteins, a-synuclein and tau, and their influence on cognitive decline in PD and related conditions.
Background:
When proteins like a-synuclein and tau accumulate together within neurons, they contribute to rapid cognitive decline in patients with PD dementia and Dementia with Lewy bodies. This project will investigate the epigenetic mechanism (the process by which genes are regulated and expressed), responsible for the exacerbation of cognitive decline in the presence of a-synuclein and tau. By studying this mechanism, we hope to uncover insights into how modifying gene expression through epigenetic modulation can potentially protect neurons from the detrimental effects of a-synuclein and its associated changes. Our research aims to identify strategies that promote resilience in neurons affected by a-synuclein pathology, with the goal of developing new therapeutic approaches.
Methods/Design:
A cell model and a mouse model will be used in this research. Primary hippocampal neurons obtained from mice will be exposed to a-synuclein and tau proteins derived from humans, allowing the co-pathology of a-synuclein and tau to be studied. We will also inject the same proteins into mice. By utilizing both models, we hope to gain a better understanding of the epigenetic mechanisms underlying PD. We will also use these models to explore the effects of a metabolic protein that regulates gene expression that we are testing to prevent cognitive decline and improve function.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This study aims to investigate the potential benefits of a promising epigenetic protein for PD-associated cognitive decline. Additionally, by studying how a-synuclein affects gene regulation related to neuronal dysfunction, we hope to uncover valuable insights that can be used to develop precise and targeted therapies for PD and related disorders. This research has the potential to make significant contributions to the diagnosis and treatment of PD, potentially leading to improved quality of life for affected individuals.