Zhou Li, Chen Di, Huang Xu-Ming, Long Fei, Cai Hua, Yao Wen-Xia, Chen Zhong-Cheng, Liao Zhi-Jian, Deng Zhe-Zhi, Tan Sha, Shan Yi-Long, Cai Wei, Wang Yu-Ge, Yang Ri-Hong, Jiang Nan, Peng Tao, Hong Ming-Fan, Lu Zheng-Qi
Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Rehabilitation, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China.
Front Cell Neurosci. 2017 Sep 29;11:281. doi: 10.3389/fncel.2017.00281. eCollection 2017.
β-Amyloid protein (Aβ) is thought to cause neuronal loss in Alzheimer's disease (AD). Aβ treatment promotes the re-activation of a mitotic cycle and induces rapid apoptotic death of neurons. However, the signaling pathways mediating cell-cycle activation during neuron apoptosis have not been determined. We find that Wnt5a acts as a mediator of cortical neuron survival, and Aβ promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aβ treated cortical neurons. Furthermore, Wnt5a signals through the non-canonical Wnt/Ca pathway to suppress cyclin D1 expression and negatively regulate neuronal cell-cycle activation in a cell-autonomous manner. Together, aberrant downregulation of Wnt5a signaling is a crucial step during Aβ induced cortical neuron apoptosis and might contribute to AD-related neurodegeneration.
β-淀粉样蛋白（Aβ）被认为会导致阿尔茨海默病（AD）中的神经元丧失。Aβ处理会促进有丝分裂周期的重新激活，并诱导神经元的快速凋亡死亡。然而，介导神经元凋亡期间细胞周期激活的信号通路尚未确定。我们发现Wnt5a作为皮质神经元存活的介质，而Aβ通过下调Wnt5a的表达促进皮质神经元凋亡。细胞周期激活是由Wnt5a在Aβ处理的皮质神经元中降低的抑制作用介导的。此外，Wnt5a通过非经典Wnt/Ca途径发出信号，以抑制细胞周期蛋白D1的表达，并以细胞自主方式负调节神经元细胞周期激活。总之，Wnt5a信号的异常下调是Aβ诱导皮质神经元凋亡过程中的关键步骤，可能导致与AD相关的神经退行性变。
