Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Bosn J Basic Med Sci. 2018 Aug 1;18(3):224-233. doi: 10.17305/bjbms.2017.2248.
Accumulating evidence indicates that neurotrophic factor-like substances involved in the induction of neurotrophic factor synthesis may aid in the treatment of neurological disorders, such as Alzheimer's disease. Yokukansan (YKS), a traditional Kampo medicine, has been used for the treatment of anxiety and mood disorders. In the present study, we aimed to identify the signaling pathways associated with YKS-mediated enhancement of nerve growth factor (NGF)-induced neurite extension in rat pheochromocytoma (PC12) cells. Akt and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation levels were assessed by western blot analysis, in the presence of YKS and following the treatment with TrkA inhibitor, K252a. YKS treatment (NGF+YKS 0.5 group) enhanced NGF-induced neurite outgrowth and phosphorylation/activation of Akt and ERK1/2 in PC12 cells. Moreover, YKS-induced effects were inhibited by the treatment with the TrkA receptor antagonist K252a (NGF+YKS 0.5+K252a group); no significant difference in neurite outgrowth was observed between K252a-treated (NGF+YKS 0.5+K252a group) and NGF-K252a-treated cells (NGF+K252a group). However, neurite outgrowth in K252a-treated cells (NGF+K252a and NGF+YKS 0.5+K252a group) reached only one-third of the level in NGF-treated cells (NGF group). NGF-mediated Akt phosphorylation increased by YKS was also inhibited by K252a treatment (NGF+YKS 0.5+K252a group), but no significant difference in ERK1/2 phosphorylation was observed between NGF-YKS-K252a- and NGF-treated cells (NGF group). Our results indicate that YKS treatment enhanced NGF-induced neurite outgrowth via induction of Akt and ERK1/2 phosphorylation, following the binding of NGF to the TrkA receptor. These findings may be useful in the development of novel therapeutic strategies for the treatment of Alzheimer's disease.
越来越多的证据表明，参与诱导神经营养因子合成的神经营养因子样物质可能有助于治疗神经退行性疾病，如阿尔茨海默病。一贯煎（YKS）是一种传统的汉方药，已被用于治疗焦虑和情绪障碍。在本研究中，我们旨在确定与 YKS 介导的增强神经生长因子（NGF）诱导的大鼠嗜铬细胞瘤（PC12）细胞突起延伸相关的信号通路。通过 Western blot 分析评估 Akt 和细胞外调节激酶 1/2（ERK1/2）的磷酸化水平，存在 YKS 并在用 TrkA 抑制剂 K252a 处理后。YKS 处理（NGF+YKS 0.5 组）增强了 NGF 诱导的 PC12 细胞突起生长以及 Akt 和 ERK1/2 的磷酸化/激活。此外，YKS 诱导的作用被 TrkA 受体拮抗剂 K252a（NGF+YKS 0.5+K252a 组）的处理所抑制；在 K252a 处理的细胞（NGF+YKS 0.5+K252a 组）和 NGF-K252a 处理的细胞（NGF+K252a 组）之间，突起生长没有观察到显着差异。然而，在 K252a 处理的细胞（NGF+K252a 和 NGF+YKS 0.5+K252a 组）中的突起生长仅达到 NGF 处理的细胞（NGF 组）的三分之一水平。YKS 处理增加的 NGF 介导的 Akt 磷酸化也被 K252a 处理（NGF+YKS 0.5+K252a 组）抑制，但在 NGF-YKS-K252a-和 NGF 处理的细胞（NGF 组）之间，ERK1/2 磷酸化没有观察到显着差异。我们的结果表明，YKS 处理通过 NGF 与 TrkA 受体结合后诱导 Akt 和 ERK1/2 磷酸化，增强了 NGF 诱导的突起生长。这些发现可能有助于开发治疗阿尔茨海默病的新治疗策略。
