叉头框蛋白O3a在神经退行性疾病中靶向研究进展

Progress in targeted research of forkhead box protein O3a in degenerative disease

神经退行性疾病是大脑或脊髓内特定神经元细胞群的丢失或进程性病变而导致的不可逆的神经功能障碍性疾病。神经炎症、氧化应激、线粒体功能障碍、兴奋性毒性和蛋白质聚集可促进神经退行性病变过程。叉头框蛋白O3a(FoxO3a)是Forkhead转录因子FoxO亚家族的一个重要成员,通过磷酸化、泛素化介导的降解、微信号转导以及相关蛋白通路,在细胞增殖、凋亡、自噬、活性氧(ROS)解毒方面发挥着重要作用,与神经退行性疾病的发生与发展息息相关。本文重点对近年来FoxO3a在神经退行性疾病中的作用机制及相关通路的靶向作用进行阐述,旨在为该病的防治提供新的研究思路。

Neurodegenerative diseases are irreversible neurological disorders caused by the loss or progres⁃sion lesion of specific neuronal cell populations in the brain or spinal cord.Neuroinflammation,oxidative stress,mitochondrial dysfunction,excitotoxicity,and protein may aggregation contribute to neurodegenerative processes.FoxO3a,an important member of the FoxO subfamily of Forkhead transcription factors,plays a crucial role in cell proliferation,apoptosis,autophagy and ROS detoxification through phosphorylation,ubiquitination mediated degra⁃dation,microsignal transduction and related protein pathways,which is closely related to the occurrence and devel⁃opment of neurodegenerative diseases.This article focuses on the mechanism of FoxO3a in neurodegenerative diseases and the targeting of related pathways in recent years were described,indicating that FoxO3a plays a key role in the occurrence and development of the disease,aiming to provide new research ideas for the prevention and treatment of this disease.