Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons
Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons
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DOI：
10.1007/s00702-017-1832-6
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发表时间：
2018-11
影响因子：
3.3
通讯作者：
M. Naoi;W. Maruyama;M. Shamoto‐Nagai
中科院分区：
文献类型：
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作者：
M. Naoi;W. Maruyama;M. Shamoto‐Nagai
A型和B型单胺氧化酶（MAO-A，-B）介导和调节神经元细胞存活或死亡的细胞内信号通路。MAO-A与神经元结构、突触活动的发展和精神疾病的发作相关，包括抑郁症和反社会攻击性冲动行为。MAO-B产生过氧化氢，并在神经退行性疾病如帕金森病和阿尔茨海默病的神经元损失中起重要作用。本文综述了MAO-A和B及其底物和抑制剂以及过氧化氢在脑功能和神经元存活与死亡中的新作用。MAO-A活性不仅受遗传因素的调节，还受环境因素的调节，包括应激、激素失调和食物因素。MAO-A活性受遗传-环境因素的影响而波动，调节神经元对刺激的反应，并影响行为和情绪活动。MAO-B抑制剂司来吉兰和雷沙吉兰通过增加人神经母细胞瘤SH-SY 5 Y和胶质母细胞瘤U118 MG细胞系中抗凋亡Bcl-2和促存活神经营养因子的表达来保护神经元。MAO-A敲低抑制了SH-SY 5 Y细胞中雷沙吉兰诱导的基因表达，而MAO-B沉默增强了U118 MG细胞中基础和司来吉兰诱导的基因表达。MAO-A和B被证明分别作为基因表达的介体或阻遏物起作用。进一步研究MAO-A和B调控信号通路的细胞机制，将有助于我们对MAO在神经元命运决定中的作用有新的认识，并有望为神经精神疾病的治疗提供新的思路。
Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of neuronal architecture, synaptic activity, and onset of psychiatric disorders, including depression, and antisocial aggressive impulsive behaviors. MAO-B produces hydrogen peroxide and plays a vital role in neuronal loss of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. This review presents a novel role of MAO-A and B, their substrates and inhibitors, and hydrogen peroxide in brain function and neuronal survival and death. MAO-A activity is regulated not only by genetic factor, but also by environmental factors, including stress, hormonal deregulation, and food factors. MAO-A activity fluctuates by genetic–environmental factors, modulates the neuronal response to the stimuli, and affects behavior and emotional activities. MAO-B inhibitors selegiline and rasagiline protect neurons via increase expression of anti-apoptotic Bcl-2 and pro-survival neurotrophic factors in human neuroblastoma SH-SY5Y and glioblastoma U118MG cell lines. MAO-A knockdown suppressed the rasagiline-induced gene expression in SH-SY5Y cells, whereas MAO-B silencing enhanced the basal- and selegiline-induced gene expression in U118MG cells. MAO-A and B were shown to function as a mediator or repressor of gene expression, respectively. Further study on cellular mechanism underlying regulation of signal pathways by MAO-A and B may bring us a new insight on the role of MAOs in decision of neuronal fate and the development of novel therapeutic strategy may be expected for neuropsychiatric disorders.