Disturbed redox homeostasis and oxidative stress: Potential players in the developmental regression in Rett syndrome

Publication date: Available online 9 January 2019Source: Neuroscience & Biobehavioral ReviewsAuthor(s): Michael MüllerAbstractRett 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.

Source: Neuroscience and Biobehavioral Reviews - January 10, 2019 Category: Neuroscience Source Type: research