Profiling and Elucidating Molecular Mechanism of Neurodegeneration in Parki

  • Yue, Zhenyu Z (PI)
  • Yang, Nan N (CoPI)
  • Crary, John (CoPI)
  • Wu, Zhuhao Z. (CoPI)
  • Blanchard, Joel J. (CoPI)
  • Zhang, Bin B (CoPI)

Project Details


The goal of our Research Center is to characterize cell-diversity at Parkinson's disease (PD)-associated brain region, elucidate molecular mechanism for vulnerability and resilience of dopaminergic (DA) neurons, and identify neuroprotective strategies for the purpose of treating PD. The major pathological hallmark of PD is the selective loss of DA neurons with poorly understood mechanisms. To address the unmet challenges, we have recently completed the largest study by-far profiling a third of million cells from a specific human brain region that is vulnerable in PD. We developed a comprehensive atlas of gene expression in many different cell types and characterized the altercations in gene expression at single cell-type levels in PD brains. We identified multiple different types of DA neurons in aged human brains and showed that their numbers are significantly reduced in PD. However, pathological evidence showed that some DA neurons persist through many years after the onset of the motor symptoms and demonstrate resilience. Here we will investigate the physiological functions of the distinctive types of DA neurons and characterize the molecular mechanism of vulnerability and resilience by using three different biological systems: human postmortem tissues, genetic mouse models, and induced human DA neuron cultures. We have assembled a team of investigators consisting of established and junior faculty members from Icahn School of Medicine at Mount Sinai. Their expertise is diverse but highly integrated and complementary to each other. The outcome of our Center program is expected to advance the understanding of DA neuron diversity and the underpinning of their vulnerability and resilience. We expect to identify key genetic and network factors, by manipulation of which we will develop strategies to overcome the vulnerability or promote the resilience of DA neurons in the SN as well as therapeutic ideas to treat PD.
Effective start/end date30/06/2230/06/26


  • Parkinson's Foundation: $2,000,000.00


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