Müller Michael, Can Karolina
*Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Zentrum Physiologie und Pathophysiologie, Institut für Neuro- und Sinnesphysiologie, Georg-August-Universität Göttingen, Universitätsmedizin, Humboldtallee 23, D-37073 Göttingen, Germany.
Biochem Soc Trans. 2014 Aug;42(4):959-64. doi: 10.1042/BST20140071.
RTT (Rett syndrome) is a severe progressive neurodevelopmental disorder with a monogenetic cause, but complex and multifaceted clinical appearance. Compelling evidence suggests that mitochondrial alterations and aberrant redox homoeostasis result in oxidative challenge. Yet, compared with other severe neuropathologies, RTT is not associated with marked neurodegeneration, but rather a chemical imbalance and miscommunication of neuronal elements. Different pharmacotherapies mediate partial improvement of conditions in RTT, and also antioxidants or compounds improving mitochondrial function may be of potential merit. In the present paper, we summarize findings from patients and transgenic mice that point towards the nature of RTT as a mitochondrial disease. Also, open questions are addressed that require clarification to fully understand and successfully target the associated cellular redox imbalance.
雷特综合征(RTT)是一种由单基因引起的严重进行性神经发育障碍,但临床表现复杂多样。有力证据表明,线粒体改变和异常的氧化还原稳态会导致氧化应激。然而,与其他严重神经病理学相比,RTT与明显的神经退行性变无关,而是与神经元成分的化学失衡和通讯障碍有关。不同的药物疗法可部分改善RTT的病情,抗氧化剂或改善线粒体功能的化合物也可能具有潜在价值。在本文中,我们总结了来自患者和转基因小鼠的研究结果,这些结果表明RTT本质上是一种线粒体疾病。此外,还提出了一些开放性问题,需要加以澄清,以便充分理解并成功针对相关的细胞氧化还原失衡。