Georg-August-Universität Göttingen, Universitätsmedizin Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Humboldtallee 23, D-37073 Göttingen, Germany; Zentrum Physiologie und Pathophysiologie, Institut für Neuro-und Sinnesphysiologie, Humboldtallee 23, D-37073 Göttingen, Germany.
Neurosci Biobehav Rev. 2019 Mar;98:154-163. doi: 10.1016/j.neubiorev.2018.12.009. Epub 2019 Jan 9.
Rett syndrome (RTT) is a neurodevelopmental disorder affecting mostly girls. A seemingly normal initial development is followed by developmental stagnation and regression, leading to severe mental impairment with autistic features, motor dysfunction, irregular breathing and epilepsy. Currently, a cure does not exist. Due to the close association of RTT with mitochondrial alterations, cellular redox-impairment and oxidative stress, compounds stabilizing mitochondrial function, cellular redox-homeostasis, and oxidant detoxification are increasingly considered as treatment concepts. Indeed, antioxidants and free-radical scavengers ameliorate certain aspects of the complex and severe clinical presentation of RTT. To further evaluate these strategies, reliable biosensors are needed to quantify redox-conditions in brain and peripheral organs of mouse models or in patient-derived cells. Genetically-encoded redox-sensors meet these requirements. Expressed in transgenic mouse-models such as our unique Rett-redox indicator mice, they will report for any cell type desired the severity of oxidant stress throughout the various disease stages of RTT. Furthermore, these sensors will be crucial to evaluate in vitro and in vivo the outcome of mitochondria- and redox-balance targeted treatments.
雷特综合征（RTT）是一种主要影响女孩的神经发育障碍。最初的发育看似正常，随后是发育停滞和倒退，导致严重的智力障碍，伴有自闭症特征、运动功能障碍、不规则呼吸和癫痫。目前尚无治愈方法。由于 RTT 与线粒体改变、细胞氧化还原损伤和氧化应激密切相关，因此稳定线粒体功能、细胞氧化还原稳态和氧化剂解毒的化合物越来越被认为是治疗概念。事实上，抗氧化剂和自由基清除剂可以改善 RTT 复杂而严重的临床表现的某些方面。为了进一步评估这些策略，需要可靠的生物传感器来量化小鼠模型的大脑和外周器官或患者来源的细胞中的氧化还原状态。遗传编码的氧化还原传感器满足这些要求。在转基因小鼠模型（如我们独特的 Rett 氧化还原指示剂小鼠）中表达时，它们将报告任何所需细胞类型在 RTT 的各个疾病阶段的氧化剂应激的严重程度。此外，这些传感器对于评估体外和体内针对线粒体和氧化还原平衡的靶向治疗的结果至关重要。
