Department of Neurosciences, Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan.
Int Rev Neurobiol. 2011;100:85-106. doi: 10.1016/B978-0-12-386467-3.00005-4.
In Parkinson's disease, type B monoamine oxidase (MAO-B) is proposed to play an important role in the pathogenesis through production of reactive oxygen species and neurotoxins from protoxicants, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In addition, inhibitors of MAO-B protect neurons in the cellular and animal models of Parkinson's and Alzheimer's diseases. However, the role of type A MAO (MAO-A) in neuronal death and neuroprotection by MAO-B inhibitors has been scarcely elucidated. This chapter presents our recent results on the involvement of MAO-A in the activation of mitochondrial death signal pathway and in the induction of prosurvival genes to prevent cell death with MAO-B inhibitors. The roles of MAO-A in the regulation of neuronal survival and death are discussed in concern to find a novel strategy to protect neurons in age-associated neurodegenerative disorders and depression.
在帕金森病中,B 型单胺氧化酶(MAO-B)被认为通过产生活性氧物种和神经毒素(如 1-甲基-4-苯基-1,2,3,6-四氢吡啶)在发病机制中发挥重要作用。此外,MAO-B 抑制剂可保护帕金森病和阿尔茨海默病的细胞和动物模型中的神经元。然而,MAO-A 在 MAO-B 抑制剂诱导的神经元死亡和神经保护中的作用尚未得到充分阐明。本章介绍了我们最近关于 MAO-A 参与线粒体死亡信号通路激活以及诱导生存相关基因以防止 MAO-B 抑制剂诱导细胞死亡的研究结果。讨论了 MAO-A 在调节神经元存活和死亡中的作用,以期找到一种保护与年龄相关的神经退行性疾病和抑郁症相关神经元的新策略。