Yan Yu-Chen, Li Yan-Hua, Xiao Bao-Guo, Wang Jian, Xi Jian-Ying, Yu Wen-Bo
Department of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
Mol Neurobiol. 2023 Apr;60(4):1826-1835. doi: 10.1007/s12035-022-03173-y. Epub 2022 Dec 29.
Bone marrow-derived neural stem cells (BM-NSCs) have shed light on novel therapeutic approaches for PD with the potential to halt or even reverse disease progression. Various strategies have been developed to promote therapeutic efficacy via optimizing implanted cells and the microenvironment of transplantation in the central nervous system (CNS). This current study further proved that the combination of fasudil, a Rho-kinase inhibitor, and BM-NSCs exhibited a synergetic effect on restoring neuron loss in the MPTP-PD mice model. It simultaneously unveiled cellular mechanisms underlying synergistic neuron-protection effects of fasudil and BM-NSCs, which included promoting the proliferation, and migration of endogenous NSCs, and contributing to microglia shift into the M2 phenotype. Corresponding molecular mechanisms were observed, including the inhibition of inflammatory responses, the elevation of neurotrophic factors, and the induction of WNT/β-catenin and PI3K/Akt/mTOR signaling pathways. Our study provides evidence for the co-intervention of BM-NSCs and fasudil as a promising therapeutic method with enhanced efficacy in treating neurodegenerative diseases.
骨髓源性神经干细胞（BM-NSCs）为帕金森病（PD）的新型治疗方法带来了曙光，具有阻止甚至逆转疾病进展的潜力。人们已经开发出各种策略，通过优化植入细胞和中枢神经系统（CNS）移植的微环境来提高治疗效果。当前这项研究进一步证明，Rho激酶抑制剂法舒地尔与BM-NSCs联合使用，对MPTP-PD小鼠模型中神经元损失的恢复具有协同作用。它同时揭示了法舒地尔和BM-NSCs协同神经元保护作用的细胞机制，包括促进内源性神经干细胞的增殖和迁移，以及促使小胶质细胞转变为M2表型。观察到了相应的分子机制，包括炎症反应的抑制、神经营养因子的升高，以及WNT/β-连环蛋白和PI3K/Akt/mTOR信号通路的诱导。我们的研究为BM-NSCs和法舒地尔的联合干预作为一种在治疗神经退行性疾病中具有增强疗效的有前景的治疗方法提供了证据。
