Mount Sinai Receives $2 Million From Parkinson’s Foundation to Investigate Underlying Cell-Specific Mechanisms of Condition

Mount Sinai

A research team from the Yue Laboratory at the Icahn School of Medicine at Mount Sinai has been selected to receive the 2022 Parkinson’s Foundation Research Center Award, totaling $2 million.

Led by Zhenyu Yue, PhD, Alex and Shirley Aidekman Family Neurological Research Professor at Icahn Mount Sinai, the team aims to conduct deep profiling of cell diversity in a Parkinson’s disease-associated brain region called the substantia nigra. This profiling aims to uncover the molecular mechanisms of vulnerability and resilience of a particular type of brain cell in the substantia nigra, and to identify neuroprotective strategies to treat Parkinson’s disease. The initiative will involve both the Yue Laboratory and the newly established Parkinson’s Foundation Research Center at Mount Sinai.

The major pathological hallmark of Parkinson’s disease is the selective loss of dopaminergic (DA) neurons, the cells of the brain that are responsible for producing dopamine and transmitting it to other cells of the nervous system, in the substantia nigra. However, the mechanisms of this selective loss of DA neurons are poorly understood.

To bridge this knowledge gap, researchers from the Yue Laboratory recently collaborated with a group led by Bin Zhang, PhD, Willard T.C. Johnson Research Professor of Neurogenetics at Icahn Mount Sinai, to develop a comprehensive atlas of gene expression in many different cell types and characterized the alterations in gene expression at single cell-type levels. They accomplished this by profiling more than 300,000 cells from the substantia nigra collected from postmortem brain tissue from both Parkinson’s disease and control patients. They identified multiple different types of DA neurons in aged human brains and showed that their numbers are significantly reduced in those with Parkinson’s disease. Interestingly, there was also evidence that some DA neurons persisted through many years after the onset of the motor symptoms that are common among Parkinson’s disease patients, demonstrating resilience.

“Through the generous support of the Parkinson’s Foundation Research Center Award, our team will now investigate the physiological functions of the distinctive types of DA neurons and characterize the underlying molecular mechanisms of vulnerability and resilience by using three different biological systems: human postmortem tissue, genetic mouse models, and induced human DA brain cell cultures,” said Dr. Yue. “We have assembled a team of investigators whose expertise is diverse but highly integrated and complementary to one another with the common goal of advancing our knowledge of and treatment potential for Parkinson’s disease.”

Key co-investigators on this project include Nan Yang, PhD; John F. Crary, PhD; Zhuhao Wu, PHD; Joel Blanchard, PhD; and Dr. Zhang.

“Through their identification of key genetic and nework factors in this particular part of the brain, Dr. Yue and his team can then develop strategies to either overcome the vulnerability to or promote the resilience of dopaminergic neurons, setting the stage for the development of effective therapeutic treatments for this debilitating condition,” said Barbara Vickrey, MD, MPH, Henry P. and Georgette Goldschmidt Professor of Neurology at Icahn Mount Sinai and Chair of Neurology for the Mount Sinai Health System.

“We are profoundly grateful to the Parkinson’s Foundation for the investment they’ve made in the work of our team and for their continued commitment to helping people with Parkinson’s disease live better lives by improving care and advancing research towards a cure,” said Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic Affairs at Icahn Mount Sinai, and Chief Scientific Officer of the Mount Sinai Health System.

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