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Nischarin/IRAS 在中枢神经系统发育、损伤和疾病中的作用。

Contribution of Nischarin/IRAS in CNS development, injury and diseases.

机构信息

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.

出版信息

J Adv Res. 2023 Dec;54:43-57. doi: 10.1016/j.jare.2023.01.020. Epub 2023 Jan 27.

DOI:10.1016/j.jare.2023.01.020
PMID:36716956
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10703726/
Abstract

BACKGROUND

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.

AIM OF REVIEW

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.

KEY SCIENTIFIC CONCEPTS OF REVIEW

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.

摘要

背景

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。

综述目的

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。

综述的关键科学概念

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/4614aa2c9336/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/4614aa2c9336/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/ba4e55411ed8/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/449f38be7437/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/2c41f8d4e90b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/4d33d528fec7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/cf8b24120764/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/3f6f6c270069/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/88a8fe85263f/gr6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98fe/10703726/4614aa2c9336/gr8.jpg

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Nucleic Acids Res. 2022 Jan 7;50(D1):D439-D444. doi: 10.1093/nar/gkab1061.
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Prenatal exposure to di (2-ethylhexyl) phthalate causes autism-like behavior through inducing Nischarin expression in the mouse offspring.产前暴露于邻苯二甲酸二（2-乙基己基）酯通过诱导小鼠后代中 Nischarin 的表达引起自闭症样行为。
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