Inserm, U910, 27 bd. Jean Moulin, 13385 Marseille Cedex 5, France.
Behav Genet. 2010 Jan;40(1):59-75. doi: 10.1007/s10519-009-9303-y. Epub 2009 Oct 23.
Rett syndrome (RTT) is a severe postnatal neurological disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. In affected children, most biological parameters, including brain structure, are normal (although acquired microcephaly is usually present). However, in recent years, a deficit in bioaminergic metabolism has been identified at the cellular and molecular levels, in more than 200 patients. Recently available transgenic mouse strains with a defective Mecp2 gene also show abnormalities, strongly suggesting that there is a direct link between the function of the MECP2 protein and the metabolism of biogenic amines. Biogenic amines appear to have an important role in the pathophysiology of Rett syndrome, for several reasons. Firstly, biogenic amines modulate a large number of autonomic and cognitive functions. Secondly, many of these functions are affected in RTT patients. Thirdly, biogenic amines are the only neurotransmitters that have repeatedly been found to be altered in RTT patients. Importantly, pharmacological interventions can be envisaged to try to counteract the deficits observed. Here, we review the available human and mouse data and present how they have been and could be used in the development of pharmacological treatments for children affected by the syndrome. Given our current knowledge and the tools available, modulating biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of Rett syndrome patients in the short term.
雷特综合征（RTT）是一种严重的产后神经发育障碍，由甲基化CpG 结合蛋白 2（MECP2）基因突变引起。在受影响的儿童中，包括大脑结构在内的大多数生物学参数都是正常的（尽管通常存在获得性小头症）。然而，近年来在超过 200 名患者中，在细胞和分子水平上发现了生物胺代谢缺陷。最近具有缺陷 Mecp2 基因的转基因小鼠品系也表现出异常，强烈表明 MECP2 蛋白的功能与生物胺的代谢之间存在直接联系。生物胺似乎在 Rett 综合征的病理生理学中具有重要作用，原因有几个。首先，生物胺调节大量自主和认知功能。其次，许多这些功能在 RTT 患者中受到影响。第三，生物胺是唯一被反复发现改变的神经递质在 RTT 患者中。重要的是，可以设想进行药理学干预以试图对抗观察到的缺陷。在这里，我们回顾了现有的人类和小鼠数据，并展示了它们如何以及可以在开发针对受该综合征影响的儿童的药物治疗中使用。鉴于我们目前的知识和可用的工具，调节生物胺代谢可能被证明是改善 Rett 综合征患者短期生活质量的最有前途的策略。
