Xiao-Xiang Chen1, Yuan Qian2,3, Xiang-Peng Wang1, Zhi-Wei Tang1, Jiao-Tian Xu1, Hai Lin1, Zhi-Yong Yang1, Xiao-Bin Song1, Di Lu4, Jia-Zhi Guo4, Li-Gong Bian5, Yu Li1, Lei Zhou6, Xing-Li Deng1. 1. Department of Neurosurgery, 1st Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. 2. Genetic Diagnosis Center, Kunming City Women and Children Hospital, Kunming, Yunnan, China. 3. Prenatal Diagnosis Lab, 1st Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. 4. Rehabilitation Engineering Research Laboratory, Biomedicine Engineering Research Centre, Kunming Medical University, Kunming, Yunnan, China. 5. Department of Anatomy, Kunming Medical University, Kunming, Yunnan, China. 6. The Key Laboratory of Stem Cell and Regenerative Medicine of Yunnan Province, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China.
Abstract
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life. AIM: This study investigated the effect of Nurr1 on neuroinflammation and differentiation of NSCs cocultured with primary microglia in the transwell coculture system. RESULTS: The results showed that Nurr1 exerted anti-inflammatory effects and promoted the differentiation of NSCs into dopaminergic neurons. CONCLUSIONS: The results suggested that Nurr1 protects dopaminergic neurons from neuroinflammation insults by limiting the production of neurotoxic mediators by microglia and maintain the survival of transplanted NSCs. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1-overexpressed NSCs as a potential treatment of PD.
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life. AIM: This study investigated the effect of Nurr1 on neuroinflammation and differentiation of NSCs cocultured with primary microglia in the transwell coculture system. RESULTS: The results showed that Nurr1 exerted anti-inflammatory effects and promoted the differentiation of NSCs into dopaminergic neurons. CONCLUSIONS: The results suggested that Nurr1 protects dopaminergic neurons from neuroinflammation insults by limiting the production of neurotoxic mediators by microglia and maintain the survival of transplanted NSCs. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1-overexpressed NSCs as a potential treatment of PD.
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