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Abstract：
BACKGROUND: Parkinson\'s disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer\'s disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells.
METHODS: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs.
RESULTS: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms.
CONCLUSIONS: hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.
METHODS: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs.
RESULTS: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms.
CONCLUSIONS: hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.
摘要：
背景：帕金森病（PD）是最常见的神经退行性疾病之一，在阿尔茨海默病之后。PD的发作以黑质中多巴胺能神经元的丢失为特征。干细胞疗法在治疗神经退行性疾病方面具有巨大的潜力,和人鼻甲来源的干细胞（hNTSC）已被发现与间充质干细胞具有一些共同的特征。尽管Hippo信号通路最初被认为调节器官中的细胞大小,最近的研究表明，它还可以控制神经细胞的炎症。
方法：从SH-SY5Y细胞（DA样细胞）分化出多巴胺能神经元样细胞，并用碘化1-甲基-4-苯基吡啶处理以刺激反应性氧化物质（ROS）产生。进行transwell测定以验证hNTSC对Hippo途径的作用。我们建立了MPTP诱导的PD小鼠模型，并通过立体定向手术将hNTSC移植到PD小鼠的黑质中。经过五周的行为测试，通过免疫印迹和免疫染色验证脑样本,以确认hNTSC的生态位控制.
结果：体外实验表明，hNTSCs通过控制ROS介导的ER应激和海马信号通路因子，显着增加细胞存活并发挥抗炎作用。同样，体内实验证明抗炎作用和细胞存活率增加.hNTSCs移植后，PD小鼠模型显示改善的活动性和PD症状的缓解。
结论：hNTSCs通过Yes相关蛋白（YAP）/带有PDZ结合基序的转录共激活因子（TAZ），通过减少炎性细胞因子来操纵海马通路，从而提高多巴胺能神经元的存活率。在这项研究中,我们发现控制hNTSCs的生态位对PD病变有治疗作用。
方法：从SH-SY5Y细胞（DA样细胞）分化出多巴胺能神经元样细胞，并用碘化1-甲基-4-苯基吡啶处理以刺激反应性氧化物质（ROS）产生。进行transwell测定以验证hNTSC对Hippo途径的作用。我们建立了MPTP诱导的PD小鼠模型，并通过立体定向手术将hNTSC移植到PD小鼠的黑质中。经过五周的行为测试，通过免疫印迹和免疫染色验证脑样本,以确认hNTSC的生态位控制.
结果：体外实验表明，hNTSCs通过控制ROS介导的ER应激和海马信号通路因子，显着增加细胞存活并发挥抗炎作用。同样，体内实验证明抗炎作用和细胞存活率增加.hNTSCs移植后，PD小鼠模型显示改善的活动性和PD症状的缓解。
结论：hNTSCs通过Yes相关蛋白（YAP）/带有PDZ结合基序的转录共激活因子（TAZ），通过减少炎性细胞因子来操纵海马通路，从而提高多巴胺能神经元的存活率。在这项研究中,我们发现控制hNTSCs的生态位对PD病变有治疗作用。
