Monoamine oxidase inactivation: from pathophysiology to therapeutics.
Monoamine oxidase inactivation: from pathophysiology to therapeutics.
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DOI：
10.1016/j.addr.2008.06.002
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发表时间：
2008-10
影响因子：
16.1
通讯作者：
Shih, Jean C.
中科院分区：
文献类型：
--
作者：
Bortolato, Marco;Chen, Kevin;Shih, Jean C.
单胺氧化酶 (MAO) A 和 B 是线粒体结合的同工酶，可催化膳食胺和单胺神经递质（如血清素、去甲肾上腺素、多巴胺、β-苯乙胺和其他微量胺）的氧化脱氨基作用。这些分子的快速降解确保了突触神经传递的正常运作，对于情绪行为和其他大脑功能的调节至关重要。 MAO 介导的反应的副产物包括几种具有潜在神经毒性的化学物质，例如过氧化氢、氨和醛。因此，人们普遍推测这些酶的长期过度活性可能会导致线粒体损伤和神经退行性紊乱。根据这些前提，MAO 抑制剂的开发导致了多种神经精神疾病（从情绪障碍到帕金森病）治疗的重大突破。此外，MAO 敲除 (KO) 小鼠的特征表明，这种酶的失活会产生许多功能和行为改变，其中一些可能可用于治疗目的。在本文中，我们讨论了一个有趣的假设，即由任一 MAO 亚型失活引起的氧化应激减弱可能有助于 MAO 抑制剂的抗抑郁和抗帕金森病作用。这种可能性进一步凸显了 MAO 失活作为治疗精神障碍的新途径的丰富来源。
Monoamine oxidases (MAOs) A and B are mitochondrial bound isoenzymes which catalyze the oxidative deamination of dietary amines and monoamine neurotransmitters, such as serotonin, norepinephrine, dopamine, β-phenylethylamine and other trace amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional behaviors and other brain functions. The byproducts of MAO-mediated reactions include several chemical species with neurotoxic potential, such as hydrogen peroxide, ammonia and aldehydes. As a consequence, it is widely speculated that prolonged excessive activity of these enzymes may be conducive to mitochondrial damages and neurodegenerative disturbances. In keeping with these premises, the development of MAO inhibitors has led to important breakthroughs in the therapy of several neuropsychiatric disorders, ranging from mood disorders to Parkinson’s disease. Furthermore, the characterization of MAO knockout (KO) mice has revealed that the inactivation of this enzyme produces a number of functional and behavioral alterations, some of which may be harnessed for therapeutic aims. In this article, we discuss the intriguing hypothesis that the attenuation of the oxidative stress induced by the inactivation of either MAO isoform may contribute to both antidepressant and antiparkinsonian actions of MAO inhibitors. This possibility further highlights MAO inactivation as a rich source of novel avenues in the treatment of mental disorders.
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影响因子：
11.3
作者：
BROWN, CS;KENT, TA;ROSE, RM
通讯作者：
ROSE, RM
安非他明、3,4-亚甲二氧基甲基苯丙胺、麦角酸二乙酰胺和儿茶酚胺神经递质的代谢物是大鼠微量胺受体的激动剂
影响因子：
3.6
作者：
Bunzow, JR;Sonders, MS;Grandy, DK
通讯作者：
Grandy, DK
影响因子：
4.8
作者：
Chen, K;Holschneider, DP;Shih, JC
通讯作者：
Shih, JC
影响因子：
5.8
作者：
DONNELLY, CH;MURPHY, DL
通讯作者：
MURPHY, DL
影响因子：
4.8
作者：
Chen, Kevin;Cases, Olivier;Shih, Jean Chen
通讯作者：
Shih, Jean Chen