Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
J Pineal Res. 2014 Nov;57(4):427-34. doi: 10.1111/jpi.12182. Epub 2014 Oct 16.
Activation of β-catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation of β-catenin. In this study, melatonin increased β-catenin protein expression and activation in human neuroblastoma cell lines SH-SY5Y cells. Melatonin also inhibited PrP (106-126)-induced neurotoxicity and the inhibition attenuated by treatment of β-catenin inhibitor ICG-001. Activation of β-catenin blocked PrP (106-126)-mediated downregulation of anti-apoptotic protein survivin and Bcl-2. Reduction of mitochondrial membrane potential, translocation of Bax, and cytochrome c release which induced by PrP (106-126) treatment were inhibited by β-catenin activation, which contributed to prevented PrP (106-126)-induced neuronal cell death. In conclusion, β-catenin activation by melatonin prevented PrP (106-126)-induced neuronal cell death through regulating anti-apoptotic proteins and mitochondrial pathways. These results also suggest the therapeutic value of Wnt/β-catenin signaling in prion-related disorders as influenced by melatonin.
β-连环蛋白在神经元中的激活调节线粒体功能，并可预防包括阿尔茨海默病和亨廷顿病在内的蛋白质错误折叠疾病。褪黑素是松果腺的天然分泌产物，通过激活β-连环蛋白发挥神经保护作用。在这项研究中，褪黑素增加了人神经母细胞瘤细胞系 SH-SY5Y 细胞中的β-连环蛋白蛋白表达和激活。褪黑素还抑制了 PrP（106-126）诱导的神经毒性，而用 β-连环蛋白抑制剂 ICG-001 处理则减弱了这种抑制作用。β-连环蛋白的激活阻断了 PrP（106-126）介导的抗凋亡蛋白存活素和 Bcl-2 的下调。PrP（106-126）处理引起的线粒体膜电位降低、Bax 易位和细胞色素 c 释放被β-连环蛋白激活所抑制，这有助于防止 PrP（106-126）诱导的神经元细胞死亡。总之，褪黑素通过调节抗凋亡蛋白和线粒体途径，激活β-连环蛋白，防止 PrP（106-126）诱导的神经元细胞死亡。这些结果还表明，Wnt/β-连环蛋白信号通路在褪黑素影响的朊病毒相关疾病中具有治疗价值。
