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蛋白质组学揭示脆性 X 综合征的奥秘:解析分子机制与治疗途径。

Proteomics insights into fragile X syndrome: Unraveling molecular mechanisms and therapeutic avenues.

机构信息

Departments of Pediatrics and Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, United States of America.

Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, United States of America.

出版信息

Neurobiol Dis. 2024 May;194:106486. doi: 10.1016/j.nbd.2024.106486. Epub 2024 Mar 26.

DOI:10.1016/j.nbd.2024.106486
PMID:38548140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11650894/
Abstract

Fragile X Syndrome (FXS) is a neurodevelopment disorder characterized by cognitive impairment, behavioral challenges, and synaptic abnormalities, with a genetic basis linked to a mutation in the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene that results in a deficiency or absence of its protein product, Fragile X Messenger Ribonucleoprotein (FMRP). In recent years, mass spectrometry (MS) - based proteomics has emerged as a powerful tool to uncover the complex molecular landscape underlying FXS. This review provides a comprehensive overview of the proteomics studies focused on FXS, summarizing key findings with an emphasis on dysregulated proteins associated with FXS. These proteins span a wide range of cellular functions including, but not limited to, synaptic plasticity, RNA translation, and mitochondrial function. The work conducted in these proteomic studies provides a more holistic understanding to the molecular pathways involved in FXS and considerably enhances our knowledge into the synaptic dysfunction seen in FXS.

摘要

脆性 X 综合征(FXS)是一种神经发育障碍,其特征是认知障碍、行为挑战和突触异常,其遗传基础与 FMR1(脆性 X 信使核糖核蛋白 1)基因的突变有关,该突变导致其蛋白产物脆性 X 信使核糖核蛋白(FMRP)缺失或缺乏。近年来,基于质谱(MS)的蛋白质组学已成为揭示 FXS 潜在复杂分子图谱的有力工具。本综述全面概述了 FXS 的蛋白质组学研究,总结了关键发现,重点介绍了与 FXS 相关的失调蛋白。这些蛋白涉及广泛的细胞功能,包括但不限于突触可塑性、RNA 翻译和线粒体功能。这些蛋白质组学研究中的工作为参与 FXS 的分子途径提供了更全面的理解,并极大地增强了我们对 FXS 中所见的突触功能障碍的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6196/11650894/46e11136a80e/nihms-2039338-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6196/11650894/8c2330c1d991/nihms-2039338-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6196/11650894/46e11136a80e/nihms-2039338-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6196/11650894/8c2330c1d991/nihms-2039338-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6196/11650894/46e11136a80e/nihms-2039338-f0002.jpg

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ACS Chem Neurosci. 2024 Jan 3;15(1):119-133. doi: 10.1021/acschemneuro.3c00497. Epub 2023 Dec 18.
2
Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development.物种特异性 FMRP 对 RACK1 的调节对产前皮质发育至关重要。
Neuron. 2023 Dec 20;111(24):3988-4005.e11. doi: 10.1016/j.neuron.2023.09.014. Epub 2023 Oct 10.
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Children With Fragile X Syndrome Display a Switch Towards Fast Fibres in Their Recruitment Strategy During Gait.患有脆性X综合征的儿童在步态过程中,其募集策略会转向快肌纤维。
J Intellect Disabil Res. 2025 Jul;69(7):582-591. doi: 10.1111/jir.13238. Epub 2025 Apr 8.
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bioRxiv. 2024 Jun 24:2024.06.19.599752. doi: 10.1101/2024.06.19.599752.
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