Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA.
Sci Rep. 2017 Jul 11;7(1):5126. doi: 10.1038/s41598-017-05287-z.
Oxidative stress is damaging to cells and contributes to aging and neurodegenerative disease. This state is mediated by production of imbalanced molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The glyoxalase pathway is an antioxidant defense system utilized to detoxify methylglyoxal and neutralize free radicals. Pathway dysfunction leads to overproduction and accumulation of toxic, prooxidant compounds. We hypothesize flavonoid treatment as a means to enhance the glyoxalase pathway's ability to detoxify in neurons. This study found that flavonoid treatment in methylglyoxal treated cerebellar neurons increased the functioning of glyoxalase pathway by enhancing expression of glyoxalase-1 and glyoxalase-2 proteins, decreased cell death and increased cellular viability. Flavonoids also significantly contributed in the retention of synaptic functions (VGLUT1 and GAD65) in cerebellar neurons. In addition, flavonoids were found to be involved in pAkt - NF-κB signaling pathway through a reduction in phosphorylation of Akt. The data here show flavonoid compounds have the potential to protect the brain from aging and neurodegenerative disease.
氧化应激会损害细胞，并导致衰老和神经退行性疾病。这种状态是由不平衡分子的产生和反应性二羰基化合物（主要是甲基乙二醛）介导的。 甘油醛酶途径是一种抗氧化防御系统，用于解毒甲基乙二醛和中和自由基。途径功能障碍会导致有毒、促氧化剂化合物的过度产生和积累。我们假设黄酮类化合物治疗是增强神经元中甘油醛酶途径解毒能力的一种手段。这项研究发现，用甲基乙二醛处理小脑神经元时，黄酮类化合物治疗可通过增强甘油醛酶-1 和甘油醛酶-2 蛋白的表达来提高甘油醛酶途径的功能，减少细胞死亡并提高细胞活力。黄酮类化合物还可显著维持小脑神经元中的突触功能（VGLUT1 和 GAD65）。此外，还发现黄酮类化合物通过降低 Akt 的磷酸化参与 pAkt-NF-κB 信号通路。这些数据表明，黄酮类化合物有可能保护大脑免受衰老和神经退行性疾病的影响。
