Johnson Shakevia, Tazik Shawna, Lu Deyin, Johnson Chandra, Youdim Moussa B H, Wang Junming, Rajkowska Grazyna, Ou Xiao-Ming
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center Jackson, MS, USA.
Front Neurosci. 2010 Nov 2;4:180. doi: 10.3389/fnins.2010.00180. eCollection 2010.
Stress detrimentally affects the brain and body and can lead to or be accompanied by depression. Although stress and depression may contribute to each other, the exact molecular mechanism underlying the effects is unclear. However, there is a correlation between stress and an increase in glucocorticoid secretion which causes a subsequent increase in monoamine oxidase (MAO) activity during stress. Consequently, MAO inhibitors have been used as traditional antidepressant drugs. Cellular treatment with the synthetic glucocorticoid, dexamethasone (a cellular stressor), has been reported to markedly increase both MAO A and MAO B catalytic activities, as well as apoptosis. This study compares the neuroprotective abilities of M30 (a new generation inhibitor of both MAO A and MAO B) with rasagiline (Azilect(®), another new MAO B inhibitor) and selegiline (Deprenyl(®), a traditional MAO B inhibitor) in the prevention of dexamethasone-induced brain cell death and MAO activity in human neuroblastoma cells, SH-SY5Y. M30 demonstrated the highest inhibitory effect on MAO A; however, M30 showed the lowest inhibitory effect on MAO B enzymatic activity in comparison to rasagiline and selegiline. Although, M30 exhibited the greatest neuroprotective effect by decreasing cell death rates and apoptotic DNA damage compared to rasagiline and selegiline, these neuroprotective effects of M30 were, overall, similar to rasagiline. Summarily, M30 has a generally greater impact on neuroprotection than the MAO B inhibitors, selegiline and rasagiline. Our results suggest that M30 may have great potential in alleviating disorders involving increases in both MAO A and MAO B, such as stress-induced disorders.
压力会对大脑和身体产生不利影响，并可能导致抑郁或伴有抑郁。尽管压力和抑郁可能相互影响，但其中的确切分子机制尚不清楚。然而，压力与糖皮质激素分泌增加之间存在关联，这会导致压力期间单胺氧化酶（MAO）活性随之升高。因此，MAO抑制剂已被用作传统抗抑郁药物。据报道，用合成糖皮质激素地塞米松（一种细胞应激源）进行细胞处理，可显著提高MAO A和MAO B的催化活性以及细胞凋亡率。本研究比较了M30（新一代MAO A和MAO B双重抑制剂）与雷沙吉兰（Azilect®，另一种新型MAO B抑制剂）和司来吉兰（Deprenyl®，一种传统MAO B抑制剂）在预防地塞米松诱导的人神经母细胞瘤细胞SH-SY5Y死亡及MAO活性方面的神经保护能力。M30对MAO A的抑制作用最强；然而，与雷沙吉兰和司来吉兰相比，M30对MAO B酶活性的抑制作用最弱。尽管与雷沙吉兰和司来吉兰相比，M30通过降低细胞死亡率和凋亡性DNA损伤表现出最大的神经保护作用，但M30的这些神经保护作用总体上与雷沙吉兰相似。总之，M30对神经保护的总体影响大于MAO B抑制剂司来吉兰和雷沙吉兰。我们的结果表明，M30在缓解涉及MAO A和MAO B均升高的疾病（如压力诱导的疾病）方面可能具有巨大潜力。
