Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou 310015, China.
Department of Basic Medicine Sciences, and Department of Orthopaedics of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Adv Res. 2023 Dec;54:43-57. doi: 10.1016/j.jare.2023.01.020. Epub 2023 Jan 27.
Murine Nischarin and its human homolog IRAS are scaffold proteins highly expressed in the central nervous system (CNS). Nischarin was initially discovered as a tumor suppressor protein, and recent studies have also explored its potential value in the CNS. Research on IRAS has largely focused on its effect on opioid dependence. Although the role of Nischarin/IRAS in the physiological function and pathological process of the CNS has gradually attracted attention and the related research results are expected to be applied in clinical practice, there is no systematic review of the role and mechanisms of Nischarin/IRAS in the CNS so far.
This review will systematically analyze the role and mechanism of Nischarin/IRAS in the CNS, and provide necessary references and possible targets for the treatment of neurological diseases, thereby broadening the direction of Nischarin/IRAS research and facilitating clinical translation.
The pathophysiological processes affected by dysregulation of Nischarin/IRAS expression in the CNS are mainly introduced, including spinal cord injury (SCI), opioid dependence, anxiety, depression, and autism. The molecular mechanisms such as factors regulating Nischarin/IRAS expression and signal transduction pathways regulated by Nischarin/IRAS are systematically summarized. Finally, the clinical application of Nischarin/IRAS has been prospected.
鼠 Nischarin 及其同源蛋白人类 IRAS 是在中枢神经系统(CNS)中高度表达的支架蛋白。Nischarin 最初被发现是一种肿瘤抑制蛋白,最近的研究也探索了其在 CNS 中的潜在价值。对 IRAS 的研究主要集中在其对阿片类药物依赖的影响上。尽管 Nischarin/IRAS 在 CNS 的生理功能和病理过程中的作用逐渐引起关注,并且相关的研究结果有望应用于临床实践,但迄今为止,还没有关于 Nischarin/IRAS 在 CNS 中的作用和机制的系统评价。
本综述将系统分析 Nischarin/IRAS 在 CNS 中的作用和机制,为治疗神经疾病提供必要的参考和可能的靶点,从而拓宽 Nischarin/IRAS 研究的方向,促进临床转化。
主要介绍了 CNS 中 Nischarin/IRAS 表达失调所影响的病理生理过程,包括脊髓损伤(SCI)、阿片类药物依赖、焦虑、抑郁和自闭症。系统总结了调节 Nischarin/IRAS 表达的因素和受 Nischarin/IRAS 调节的信号转导途径等分子机制。最后,对 Nischarin/IRAS 的临床应用进行了展望。