Zhang Can, Ge Xuemei, Lok Kenghoe, Zhao Lu, Yin Ming, Wang Ze-Jian
School of Pharmacy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China.
Cell Mol Neurobiol. 2014 Apr;34(3):409-17. doi: 10.1007/s10571-014-0026-0. Epub 2014 Jan 11.
Alzheimer's disease (AD) is characterized by deposition of beta-amyloid peptides (Aβ) and progressive loss of neurons. Neural stem/progenitor cells (NSPCs) can proliferate and produce immature neurons even in the brain of AD patients. However, Aβ42 significantly decreased the expression of RhoC in NSPCs during the co-incubation (P < 0.01). Treating with RhoC siRNA prevented membrane from protrusion and led to a significant reduction in cell migration in responses to SDF-1. Compared with wild-type mice, the numbers of RhoC-immunoreactive cells in hippocampus and cortex were significantly down-regulated in APP/PS1 mice aged 9 months. The results suggest that Aβ42 down-regulates the expression of RhoC in NSPCs in vitro and in vivo; down-regulated RhoC expression results in decreased migration of NSPCs.
阿尔茨海默病(AD)的特征是β-淀粉样肽(Aβ)沉积和神经元的进行性丧失。即使在AD患者的大脑中,神经干/祖细胞(NSPCs)也能增殖并产生未成熟的神经元。然而,在共孵育期间,Aβ42显著降低了NSPCs中RhoC的表达(P<0.01)。用RhoC小干扰RNA处理可防止细胞膜突出,并导致对基质细胞衍生因子-1(SDF-1)反应的细胞迁移显著减少。与野生型小鼠相比,9月龄APP/PS1小鼠海马和皮质中RhoC免疫反应性细胞的数量显著下调。结果表明,Aβ42在体外和体内均下调NSPCs中RhoC的表达;RhoC表达下调导致NSPCs迁移减少。