神经发育中的染色质修饰因子

Chromatin modifiers in neurodevelopment.

作者信息

Rezazadeh Sarallah, Ji Hong, Giulivi Cecilia

机构信息

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.

出版信息

Front Mol Neurosci. 2025 May 21;18:1551107. doi: 10.3389/fnmol.2025.1551107. eCollection 2025.

Abstract

Emerging sequencing studies highlight the critical role of chromatin regulatory mechanisms in human diseases, particularly in neurodevelopmental and neurological disorders. Insights gained from these studies and model organism research reveal the intricate involvement of chromatin regulators in neurodevelopment, raising compelling questions about how mutations in these ubiquitous proteins drive specific dysfunctions in the nervous system. This mini review delves into key chromatin modifiers, including the histone methyl transferases NSD1 and ASH1L, the methyl-CpG-binding repressor MeCP2, and the enzymatic repressor EZH2. While functions of these proteins are relatively well-studied, the roles of many other chromatin modifiers in neurodevelopment remain poorly understood. Existing therapies targeting chromatin modifiers have shown promise, with some achieving significant clinical success. The possibility that neurological dysfunctions may be treatable even later in life underscores the urgency of prioritizing chromatin modifiers as therapeutic targets. In this mini review, we critically evaluate the current understanding of chromatin modifiers, focusing on methylation, and spotlight their pivotal roles in early brain development and neurological disorders. By advancing this field, we aim to inspire progress toward innovative treatments for these challenging conditions.

摘要

新兴的测序研究突出了染色质调控机制在人类疾病中的关键作用,尤其是在神经发育和神经疾病方面。从这些研究以及模式生物研究中获得的见解揭示了染色质调节因子在神经发育中的复杂参与,引发了关于这些普遍存在的蛋白质中的突变如何导致神经系统特定功能障碍的紧迫问题。本综述探讨了关键的染色质修饰因子,包括组蛋白甲基转移酶NSD1和ASH1L、甲基CpG结合抑制因子MeCP2以及酶抑制因子EZH2。虽然这些蛋白质的功能已得到相对充分的研究,但许多其他染色质修饰因子在神经发育中的作用仍知之甚少。现有的针对染色质修饰因子的疗法已显示出前景,其中一些已取得显著的临床成功。神经功能障碍甚至在生命后期也可能可治疗的可能性凸显了将染色质修饰因子作为治疗靶点的紧迫性。在本综述中,我们批判性地评估了目前对染色质修饰因子的理解,重点关注甲基化,并突出它们在早期脑发育和神经疾病中的关键作用。通过推动该领域的发展,我们旨在激发针对这些具有挑战性疾病的创新治疗方法取得进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26ed/12133960/d1b0f192821b/fnmol-18-1551107-g001.jpg

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