Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence.
Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence.
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DOI：
10.1016/b978-0-12-386467-3.00002-9
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发表时间：
2011
影响因子：
--
通讯作者：
Shih, Jean C.
中科院分区：
文献类型：
--
作者：
Bortolato, Marco;Shih, Jean C.
单胺氧化酶(MAO)同工酶A和B是线粒体结合蛋白，催化单胺类神经递质和异物胺的氧化脱氨反应。虽然它们起源于一个共同的祖先基因，位于X染色体上，并显示出70%的结构相似性，但它们的底物偏好、区域分布和生理作用是不同的。事实上，虽然MAO-A对5-羟色胺和去甲肾上腺素有很高的亲和力，但MAO-B主要服务于2-苯乙胺(PEA)的分解代谢，并有助于其他微量胺和多巴胺的降解。临床前和临床证据的趋同表明，MAO酶活性的变化-无论是由于遗传因素还是环境因素-可以对行为调节产生深远影响，并在从反社会人格障碍到帕金森氏症等一系列精神和神经退行性疾病的病理生理学中发挥作用。在过去的几年里，我们在理解与编码这两种同工酶的基因的遗传多态和突变相关的表型变异方面取得了许多进展。特别是，关于MAO缺陷小鼠表型的新发现突显了这两种同工酶在从自闭症和焦虑到冲动控制障碍和ADHD等广泛的精神障碍中的新的潜在含义。这些研究将为未来研究这些病理疾病的神经生物学和神经化学基础，以及基因×环境交互作用在几种精神障碍易感性中的作用奠定基础。
Monoamine oxidase (MAO) isoenzymes A and B are mitochondrial-bound proteins, catalyzing the oxidative deamination of monoamine neurotransmitters as well as xenobiotic amines. Although they derive from a common ancestral progenitor gene, are located at X-chromosome and display 70% structural identity, their substrate preference, regional distribution, and physiological role are divergent. In fact, while MAO-A has high affinity for serotonin and norepinephrine, MAO-B primarily serves the catabolism of 2-phenylethylamine (PEA) and contributes to the degradation of other trace amines and dopamine. Convergent lines of preclinical and clinical evidence indicate that variations in MAO enzymatic activity—due to either genetic or environmental factors—can exert a profound influence on behavioral regulation and play a role in the pathophysiology of a large spectrum of mental and neurodegenerative disorders, ranging from antisocial personality disorder to Parkinson’s disease. Over the past few years, numerous advances have been made in our understanding of the phenotypical variations associated with genetic polymorphisms and mutations of the genes encoding for both isoenzymes. In particular, novel findings on the phenotypes of MAO-deficient mice are highlighting novel potential implications of both isoenzymes in a broad spectrum of mental disorders, ranging from autism and anxiety to impulse-control disorders and ADHD. These studies will lay the foundation for future research on the neurobiological and neurochemical bases of these pathological conditions, as well as the role of gene × environment interactions in the vulnerability to several mental disorders.