Plants for Human Health Institute, Dept. of Animal Science, NC Research Campus, NC State University, Kannapolis, 28081, NC, USA.
Dept. of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121, Ferrara, Italy.
Free Radic Biol Med. 2020 May 20;152:100-106. doi: 10.1016/j.freeradbiomed.2020.02.023. Epub 2020 Feb 28.
Mutations in X-linked gene methyl-CpG-binding protein 2 (MECP2), a key transcriptional regulator, account for most cases of Rett syndrome (RTT), a devastating neurodevelopmental disorder with no known cure. Despite extensive research to elucidate MeCP2 functions, the mechanisms underlying RTT pathophysiology are still unclear. In addition to a variety of neurological symptoms, RTT also includes a plethora of additional phenotypical features including altered lipid metabolism, redox imbalance, immune dysfunction and mitochondrial abnormalities that explain its multisystemic nature. Here, we provide an overview of the current knowledge on the potential role of dysregulated inflammatory and immune responses in RTT. The findings show that abnormalities of humoral and cell-mediated immunity together with chronic low-grade inflammation in multiple organs represent not only clinical manifestations of RTT but rather can contribute to its development and deteriorating course. A future research challenge could be to target therapeutically immune dysfunction as a novel means for RTT management.
X 连锁基因甲基化CpG 结合蛋白 2（MECP2）的突变是大多数雷特综合征（RTT）病例的原因，RTT 是一种破坏性的神经发育障碍，目前尚无已知的治疗方法。尽管已经进行了广泛的研究来阐明 MeCP2 的功能，但 RTT 病理生理学的机制仍不清楚。除了各种神经症状外，RTT 还包括多种额外的表型特征，包括脂质代谢改变、氧化还原失衡、免疫功能障碍和线粒体异常，这解释了其多系统的性质。在这里，我们概述了目前关于失调的炎症和免疫反应在 RTT 中的潜在作用的知识。研究结果表明，体液和细胞介导免疫的异常以及多个器官的慢性低度炎症不仅是 RTT 的临床表现，而且可能有助于其发展和恶化过程。未来的研究挑战可能是将免疫功能障碍作为 RTT 治疗的一种新方法作为治疗靶点。
