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2006/2o - Abstract

Grant Information

Aging - Start-Up
The roles of Nurr1 and Pitx3 in dopaminergic differentiation of hESC
Xianmin Zeng, PhD
The Buck Institute
Funding Status
  • Completed
  • 3 years, $70,000 per year
  • 7/1/2006 to 6/30/2009


2006/2o - Abstract
Brief Summary
"The Roles of Nurr1 and Pitx3 in Dopaminergic Differentiation of hESC" Parkinson’s disease (PD) is a neurodegenerative disorder caused by the death of dopaminergic neurons in the midbrain. Despite a well-described clinical and pathological feature, the mechanisms which lead to neurodegeneration in PD remain elusive. Scientists have long realized that studies of dopaminergic neurons are important to understand these mechanisms and thereby to find a cure or to prevent PD. However, the shortage of human neurons created serious obstacles for such studies, because prior now, such neurons could only be obtained from human fetal tissues. Recent progress in utilizing human embryonic stem cells (hESCs) to create dopaminergic neurons has provided a human model available for studies without the uncertainty of guessing whether the responses of human neurons may differ from those of animals. In mice, two transcription factors, Nurr1 and Pitx3, have been found to play important roles in regulating dopaminergic development. However, it is yet to be established that they play these roles with human neurons. The objective of this proposal is to address the mechanisms and functional significance of transcription factors in regulating human dopaminergic neuronal development using hESCs. Successfully defining the roles of Nurr1 and Pitx3 may provide important information on human dopaminergic development, which in turn may provide insights into the pathology and treatment of PD. Ultimately, an understanding of the molecular events of dopaminergic development may enable the development of effective therapeutic strategies to PD. More importantly, new therapies that are found for PD are likely to be applicable to other neurodegenerative disorders like Alzheimer’s disease.

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