通过星形胶质细胞重编程治疗帕金森病:进展与挑战。
Treating Parkinson's disease by astrocyte reprogramming: Progress and challenges.
机构信息
Department of Molecular and Cellular Medicine, Institute for Regenerative Medicine, Texas A&M University Health Science Center College of Medicine, College Station, TX, USA.
出版信息
Sci Adv. 2021 Jun 23;7(26). doi: 10.1126/sciadv.abg3198. Print 2021 Jun.
Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is typified by both motor and nonmotor symptoms. The current medications provide symptomatic relief but do not stimulate the production of new dopaminergic neurons in the substantia nigra. Astrocyte reprogramming has recently received much attention as an avenue for increasing functional dopaminergic neurons in the mouse PD brain. By targeting a microRNA (miRNA) loop, astrocytes in the mouse brain could be reprogrammed into functional dopaminergic neurons. Such in vivo astrocyte reprogramming in the mouse model of PD has successfully added new dopaminergic neurons to the substantia nigra and increased dopamine levels associated with axonal projections into the striatum. This review deliberates the astrocyte reprogramming methods using specific transcription factors and mRNAs and the progress in generating dopaminergic neurons in vivo. In addition, the translational potential, challenges, and potential risks of astrocyte reprogramming for an enduring alleviation of parkinsonian symptoms are conferred.
帕金森病(PD)是第二大常见的神经退行性疾病,其特征是既有运动症状又有非运动症状。目前的药物治疗只能提供症状缓解,而不能刺激黑质中产生新的多巴胺能神经元。星形胶质细胞重编程最近受到广泛关注,被认为是增加小鼠 PD 大脑中功能性多巴胺能神经元的一种途径。通过靶向一个 microRNA(miRNA)环,可以将小鼠大脑中的星形胶质细胞重编程为功能性多巴胺能神经元。在 PD 小鼠模型中,这种体内星形胶质细胞重编程成功地将新的多巴胺能神经元添加到黑质中,并增加了与轴突投射到纹状体相关的多巴胺水平。本综述详细讨论了使用特定转录因子和 mRNAs 的星形胶质细胞重编程方法,以及在体内产生多巴胺能神经元的进展。此外,还探讨了星形胶质细胞重编程对持久缓解帕金森病症状的转化潜力、挑战和潜在风险。