The Neuroscience Laboratory, Felsenstein Medical Research Center, Petach Tikva, Tel Aviv University, Tel Aviv, Israel.
J Neurochem. 2011 Feb;116(4):522-9. doi: 10.1111/j.1471-4159.2010.07131.x. Epub 2011 Jan 24.
Neural stem cells give rise to new hippocampal neurons throughout adulthood. Defects in neurogenesis are associated with cognitive dysfunctions, such as Alzheimer disease (AD). Our understanding of the signals controlling this process is limited. The present in vitro study explored the manner in which the Wnt signaling pathway regulates the differentiation of hippocampal progenitors (HPs) into neurons under the influence of amyloid β(42) (Aβ(42) ). The results showed that oligomeric Aβ(42) reduced neuronal differentiation. This process was accompanied by a reduction in active β-catenin levels and proneural gene expression. The addition of Wnt3a increased the neuronal differentiation of Aβ(42) -treated HPs, at the expense of astrocyte differentiation. The effect of Wnt signaling was attributable to progenitor cell differentiation to the neuronal lineage, and not to increased proliferation or rescue of neurons. The interruption of Wnt signaling by oligomeric Aβ(42) may have clinical implications for the treatment of impaired neurogenesis in AD.
神经干细胞在整个成年期产生新的海马神经元。神经发生缺陷与认知功能障碍有关，如阿尔茨海默病（AD）。我们对控制这一过程的信号的理解是有限的。本体外研究探讨了 Wnt 信号通路在淀粉样β（42）（Aβ（42））影响下调节海马祖细胞（HPs）分化为神经元的方式。结果表明，寡聚体 Aβ（42）减少神经元分化。这一过程伴随着活性 β-连环蛋白水平和神经前基因表达的降低。Wnt3a 的添加增加了 Aβ（42）处理的 HPs 的神经元分化，而以星形胶质细胞分化为代价。Wnt 信号的作用归因于祖细胞向神经元谱系的分化，而不是增殖增加或神经元挽救。寡聚体 Aβ（42）对 Wnt 信号的中断可能对 AD 中受损神经发生的治疗具有临床意义。
