AUTHOR=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 

TITLE=Wnt5a Promotes Cortical Neuron Survival by Inhibiting Cell-Cycle Activation

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00281

DOI=10.3389/fncel.2017.00281

ISSN=1662-5102

ABSTRACT=<p>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<sub>42</sub> promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aβ<sub>42</sub> treated cortical neurons. Furthermore, Wnt5a signals through the non-canonical Wnt/Ca<sup>2+</sup> 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<sub>42</sub> induced cortical neuron apoptosis and might contribute to AD-related neurodegeneration.</p>